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Hanan M Alharbi Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi ArabiaCorrespondence: Hanan M Alharbi, Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia, Email hmsharbi@uqu.edu.saAbstract: The burgeoning global mortality rates attributed to cancer have precipitated a critical reassessment of conventional therapeutic modalities, most notably chemotherapy, due to their pronounced adverse effects. This reassessment has instigated a paradigmatic shift towards nanomedicine, with a particular emphasis on the potentialities of biopolymer-assisted drug delivery systems. Biopolymers, distinguished by their impeccable biocompatibility, versatility, and intrinsic biomimetic properties, are rapidly ascending as formidable vectors within the cancer theragnostic arena. This review endeavors to meticulously dissect the avant-garde methodologies central to biopolymer-based nanomedicine, exploring their synthesis, functional mechanisms, and subsequent clinical ramifications. A key focus of this analysis is the pioneering roles and efficacies of lipid-based, polysaccharide, and composite nano-carriers in enhancing drug delivery, notably amplifying the enhanced permeation and retention effect. This examination is further enriched by referencing flagship nano formulations that have received FDA endorsement, thereby underscoring the transformative potential and clinical viability of biopolymer-based nanomedicines. Furthermore, this discourse illuminates groundbreaking advancements in the realm of photodynamic therapy and elucidates the implications of advanced imaging techniques in live models. Conclusively, this review not only synthesizes current research trajectories but also delineates visionary pathways for the integration of cutting-edge biomaterials in cancer treatment. It charts a course for future explorations within the dynamic domain of biopolymer-nanomedicine, thereby contributing to a deeper understanding and enhanced application of these novel therapeutic strategies.Keywords: theragnostic, nanomedicines, antitumor, drug delivery, nanotherapeutic, anticancer, biopolymers

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood–brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures. [ABSTRACT FROM AUTHOR]

Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence‐associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D‐overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH‐responsive drug release. Moreover, SP@NNPm effectively induces PGC1α‐mediated mitochondrial biogenesis and mitigates senescence‐associated markers induced by oxidative stress and the SASP, thereby alleviating puncture‐induced senescence and disc degeneration. This dual‐targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment. [ABSTRACT FROM AUTHOR]

The clinical efficacy of current cancer therapies falls short, and there is a pressing demand to integrate new targets with conventional therapies. Autophagy, a highly conserved self-degradation process, has received considerable attention as an emerging therapeutic target for cancer. With the rapid development of nanomedicine, nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance. Hence, considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy, we outline the latest advances in autophagy-based nanotherapeutics. Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression, the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated. Further, emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways, including modulation of the mammalian target of rapamycin (mTOR) pathway, autophagy-related (ATG) and its complex expression, reactive oxygen species (ROS) and mitophagy, interference with autophagosome-lysosome fusion, and inhibition of hypoxia-mediated autophagy. In addition, combination therapies in which nano-autophagy modulation is combined with chemotherapy, phototherapy, and immunotherapy are also described. Finally, the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned. Given the potential advantages of combining autophagy as a highly regarded cancer therapeutic target with nanotechnology, this review outlines recent advances in autophagy-based nanotherapeutics for cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are cell-secreted nanovesicles that play an important role in long-range cell–cell communication. Although EVs pose a promising alternative to cell-based therapy, targeted in vivo delivery still falls short. Many studies have explored the surface modification of EVs to enhance their targeting capabilities. However, to our knowledge, there are no standardized practices to confirm the successful surface modification of EVs or calculate the degree of conjugation on EV surfaces (conjugation efficiency). These pieces of information are essential in the reproducibility of targeted EV therapeutics and the determination of optimized conjugation conditions for EVs to see significant therapeutic effects in vitro and in vivo. This review will discuss the vast array of techniques adopted, technologies developed, and efficiency definitions made by studies that have calculated EV/nanoparticle surface conjugation efficiency and how differences between studies may contribute to differently reported conjugation efficiencies. [ABSTRACT FROM AUTHOR]

Abstract Cellular senescence is a significant contributor to intervertebral disc aging and degeneration. However, the application of senotherapies, such as senomorphics targeting senescence markers and the senescence‐associated secretory phenotype (SASP), remains limited due to challenges in precise delivery. Given that the natural killer group 2D (NKG2D) ligands are increased on the surface of senescent nucleus pulposus (NP) cells, the NKG2D‐overexpressing NP cell membranes (NNPm) are constructed, which is expected to achieve a dual targeting effect toward senescent NP cells based on homologous membrane fusion and the NKG2D‐mediated immunosurveillance mechanism. Then, mesoporous silica nanoparticles carrying a peroxisome proliferator‐activated receptor‐ɣ coactivator 1α (PGC1α)inducer (SP) are coated with NNPm (SP@NNPm) and it is found that SP@NNPm selectively targets senescent NP cells, and the SP cores exhibit pH‐responsive drug release. Moreover, SP@NNPm effectively induces PGC1α‐mediated mitochondrial biogenesis and mitigates senescence‐associated markers induced by oxidative stress and the SASP, thereby alleviating puncture‐induced senescence and disc degeneration. This dual‐targeting nanotherapeutic system represents a novel approach to delivery senomorphics for disc degeneration treatment.

Due to their inhibition of acetylcholinesterase, organophosphates are among the most toxic of chemicals. Pralidoxime (a.k.a 2-PAM) is the only acetylcholinesterase reactivator approved in the U.S., but 2-PAM only poorly traverses the blood–brain barrier. Previously, we have demonstrated that scL-2PAM, a nanoformulation designed to enter the brain via receptor-mediated transcytosis, is superior to unencapsulated 2-PAM for reactivating brain acetylcholinesterase, ameliorating cholinergic crisis, and improving survival rates for paraoxon-exposed mice. Here, we employ histology and transcriptome analyses to assess the ability of scL-2PAM to prevent neurological sequelae including microglial activation, expression of inflammatory cytokines, and ultimately loss of neurons in mice surviving paraoxon exposures. Levels of the mRNA encoding chemokine ligand 2 (CCL2) were significantly upregulated after paraoxon exposures, with CCL2 mRNA levels in the brain correlating well with the intensity and duration of cholinergic symptoms. Our nanoformulation of 2-PAM was found to be superior to unencapsulated 2-PAM in reducing the levels of the CCL2 transcript. Moreover, brain histology revealed that scL-2PAM was more effective than unencapsulated 2-PAM in preventing microglial activation and the subsequent loss of neurons. Thus, scL-2PAM appears to be a new and improved countermeasure for reducing neuroinflammation and mitigating brain damage in survivors of organophosphate exposures.

Yiming Zhang,1,2,* Yiming Dou,1,2,* Yang Liu,1,2 Mingyuan Di,1,2 Hanming Bian,1,2 Xun Sun,1,2 Qiang Yang1,2 1Department of Spine Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 2Clinical School of Orthopedics, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xun Sun; Qiang Yang, Department of Spine Surgery, Tianjin Hospital, 406 Jiefang SouthRoad, Hexi District, Tianjin, 300211, People’s Republic of China, Email sunxun_tju@yeah.net; yangqiang1980@126.comAbstract: Extracellular vesicles (EVs) are nanoscale bilayer phospholipid membrane vesicles released by cells. Contained large molecules such as nucleic acid, protein, and lipid, EVs are an integral part of cell communication. The contents of EVs vary based on the cell source and play an important role in both pathological and physiological conditions. EVs can be used as drugs or targets in disease treatment, and changes in the contents of EVs can indicate the progression of diseases. In recent years, with the continuous exploration of the structure, characteristics, and functions of EVs, the potential of engineered EVs for drug delivery and therapy being constantly explored. This review provides a brief overview of the structure, characteristics and functions of EVs, summarizes the advanced application of EVs and outlook on the prospect of it. It is our hope that this review will increase understanding of the current development of medical applications of EVs and help us overcome future challenges.Keywords: extracellular vesicle, nanotherapeutic, disease diagnosis, engineered exosome, advances applications

Intrinsic drug resistance mechanisms of tumor cells often reduce intracellular drug concentration to suboptimal levels. Epithelial‐to‐mesenchymal transition (EMT) is a pivotal process in tumor progression and metastasis that confers an aggressive phenotype as well as resistance to chemotherapeutics. Therefore, it is imperative to develop novel strategies and identify new targets to improve the overall efficacy of cancer treatment. We developed SN38 (active metabolite of irinotecan)‐assembled glycol chitosan nanoparticles (cSN38) for the treatment of pancreatic ductal adenocarcinoma (PDAC). Furthermore, cSN38 and the TGF‐β1 inhibitor LY364947 formed composite nanoparticles upon self‐assembly (cSN38 + LY), which obviated the poor aqueous solubility of LY364947 and enhanced drug sensitivity. The therapeutic efficacy of cSN38 + LY nanotherapeutics was studied in vitro and in vivo using suitable models. The cSN38 nanoparticles exhibited an antitumor effect that was significantly attenuated by TGF‐β‐induced EMT. The cellular uptake of SN38 was impeded during EMT, which affected the therapeutic efficacy. The combination of LY364947 and cSN38 markedly enhanced the cellular uptake of SN38, increased cytotoxic effects, and inhibited EMT in PDAC cells in vitro. Furthermore, cSN38 + LY significantly inhibited PDAC xenograft growth in vivo. The cSN38 + LY nanoparticles increased the therapeutic efficacy of cSN38 via repressing the EMT of PDAC cells. Our findings provide a rationale for designing nanoscale therapeutics to combat PDAC. [ABSTRACT FROM AUTHOR]

Min Wei,1 Zhaofei Yang,1 Song Li,1 Weidong Le1,2 1Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116021, People’s Republic of China; 2Institute of Neurology, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of ChinaCorrespondence: Weidong Le, Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, 116021, People’s Republic of China, Email wdle@sibs.ac.cnAbstract: Neurodegeneration is characterized by progressive, disabling, and incurable neurological disorders with the massive loss of specific neurons. As one of the most promising potential therapeutic strategies for neurodegenerative diseases, stem cell therapy exerts beneficial effects through different mechanisms, such as direct replacement of damaged or lost cells, secretion of neurotrophic and growth factors, decreased neuroinflammation, and activation of endogenous stem cells. However, poor survival and differentiation rates of transplanted stem cells, insufficient homing ability, and difficulty tracking after transplantation limit their further clinical use. The rapid development of nanotechnology provides many promising nanomaterials for biomedical applications, which already have many applications in neurodegenerative disease treatment and seem to be able to compensate for some of the deficiencies in stem cell therapy, such as transport of stem cells/genes/drugs, regulating stem cell differentiation, and real-time tracking in stem cell therapy. Therefore, nanotherapeutic strategies combined with stem cell therapy is a promising therapeutic approach to treating neurodegenerative diseases. The present review systematically summarizes recent advances in stem cell therapeutics and nanotherapeutic strategies and highlights how they can be combined to improve therapeutic efficacy for the treatment of neurodegenerative diseases.Keywords: nanotherapeutic, nanomaterials, stem cell therapy, neurodegenerative diseases

Extracellular vesicles (EVs) are cell-secreted nanovesicles that play an important role in long-range cell–cell communication. Although EVs pose a promising alternative to cell-based therapy, targeted in vivo delivery still falls short. Many studies have explored the surface modification of EVs to enhance their targeting capabilities. However, to our knowledge, there are no standardized practices to confirm the successful surface modification of EVs or calculate the degree of conjugation on EV surfaces (conjugation efficiency). These pieces of information are essential in the reproducibility of targeted EV therapeutics and the determination of optimized conjugation conditions for EVs to see significant therapeutic effects in vitro and in vivo. This review will discuss the vast array of techniques adopted, technologies developed, and efficiency definitions made by studies that have calculated EV/nanoparticle surface conjugation efficiency and how differences between studies may contribute to differently reported conjugation efficiencies.

Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model in vivo was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.

Mycobacterium marinum is a waterborne pathogen responsible for tuberculosis-like infections in cold-blooded animals and is an opportunistic pathogen in humans. M. marinum is the closest genetic relative of the Mycobacterium tuberculosis complex and is a reliable surrogate for drug susceptibility testing. We synthesized and evaluated two nanoparticle (NP) formulations for compatibility with rifampicin, isoniazid, pyrazinamide, and ethambutol (PIRE), the front-line antimycobacterial drugs used in combination against active tuberculosis infections. Improved in vitro antimicrobial activity was observed with encapsulated rifampicin alone or in a cocktail of drugs formulated through co-encapsulation in amphiphilic polyanhydride NPs. Broth antimicrobial testing revealed that the encapsulation of PIRE in NP resulted in a significant increase in antimicrobial activity, with the benefit over soluble formulations at biologically relevant concentrations ranging from >10 to >3,000 fold. M. marinum-infected human macrophages treated with NP-PIRE were cleared of viable bacteria in 48 h following a single treatment, representing a >4 log reduction in colony-forming units and a >2,000-fold increase in antimicrobial activity. The amphiphilic polyanhydride nanoparticles demonstrated the ability to co-encapsulate PIRE antibiotics and enhance their antimicrobial activity against M. marinum in infected macrophages in culture and in vitro. These data suggest that polyanhydride nanoparticles are a promising nanotherapeutic for combatting Mycobacterium infections through improved intracellular targeting of encapsulated antibiotics.

Acute kidney injury (AKI) is a serious kidney disease without specific medications currently except for expensive dialysis treatment. Some potential drugs are limited due to their high hydrophobicity, poor in vivo stability, low bioavailability and possible adverse effects. Besides, kidney-targeted drugs are not common and small molecules are cleared too quickly to achieve effective drug concentrations in injured kidneys. These problems limit the development of pharmacological therapy for AKI. Nanotherapeutics based on nanotechnology have been proved to be an emerging and promising treatment strategy for AKI, which may solve the pharmacological therapy dilemma. More and more nanotherapeutics with different physicochemical properties are developed to efficiently deliver drugs, increase accumulation and control release of drugs in injury kidneys and also directly as effective antioxidants. Here, we discuss the recent nanotherapeutics applied in the treatment and prevention of AKI with improved effectiveness and few side effects.

• Neurodegenerative disorders involve neuronal loss in central nervous system. • Vector delivery is capable to develop safer and efficient gene delivery to brain. • Here various viral vector in neurodegenerative disorders has been discussed. Neurodegenerative disorders affecting a large populace involve neuronal loss in central nervous system (CNS) system. Recently, viral vector having particle size < 100 nm come up to light as an effective tool to deliver desirable gene in mutated cells by utilizing transfection ability of viruses to recover brain diseases. Vector delivery and production methods have evolved over recent years with an objective to develop safer and efficient gene delivery to brain. This review highlights different types of viral vector, virus production and their application in numerous neurodegenerative disorders. We also explored the barriers associated with this paradigm along with the future prospective. [ABSTRACT FROM AUTHOR]

The ongoing opioid crisis highlighted the need for non-steroidal anti-inflammatory drugs (NSAIDs), nonaddictive analgesics against pain, fever, and inflammation. However, NSAIDs may cause gastrointestinal and cardiovascular adverse effects. To avoid systemic toxicity and deliver drugs to diseased tissues, nanotechnology methods of NSAID encapsulation have been reported and some have reached clinical development. Currently, 57 micro- and nanodrugs are approved by the US FDA. Already approved nanoanalgesics have revealed superior efficacy or reduced toxicity compared with placebo or lower doses of systemically administered active comparators. In this review, the evidence for approval of the marketed nanodrugs will be discussed, with a focus on therapies for pain and inflammation. Nanomedicine remains an attractive field for the development of targeted analgesics. Despite the unmet medical need for nonaddictive analgesics, only a small fraction of nanocarrier-based drugs has been approved for pain and inflammation, notably, not a single non-steroidal anti-inflammatory drug (NSAID). Nanotechnology-based analgesic and anti-inflammatory drugs were FDA-approved in small trials and showed superiority in comparison with placebo or an active comparator at less than a clinically effective dose. For analgesics with addictive potential, nanotechnology aims to develop abuse-deterrent formulations (ADFs) of prescription opioids. It remains to be seen if opioids in tamper-resistant nanocarriers will have the same analgesic efficacy but reduced abuse potential than the conventional formulations. Nano-NSAIDs actively targeted to the cells secreting pro-inflammatory mediators, like prostaglandin E 2 (PGE 2), may present a therapeutic advantage over passively targeted or systemic drugs in chronic pain conditions. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments. Additionally, the difficulty of ensuring drugs effectively cross the natural blood–brain barrier (BBB) substantially reduces treatment efficiency. These conditions concomitantly limit the efficacy of standard chemotherapeutic agents available for GB. Indeed, there is an urgent need of a multifunctional drug vehicle system that has potential to transport anticancer drugs efficiently to the target and can successfully cross the BBB. In this review, we summarize some nanoparticle (NP)-based therapeutics attached to GB cells with antigens and membrane receptors for site-directed drug targeting. Such multicore drug delivery systems are potentially biodegradable, site-directed, nontoxic to normal cells and offer long-lasting therapeutic effects against brain cancer. These models could have better therapeutic potential for GB as well as efficient drug delivery reaching the tumor milieu. The goal of this article is to provide key considerations and a better understanding of the development of nanotherapeutics with good targetability and better tolerability in the fight against GB.

High-density lipoprotein (HDL) serves as a natural nanoparticle with compositional and functional heterogeneity and contributes to the maintenance of lipid metabolism and various biological functions. HDL also transports endogenous microRNAs, vitamins, hormones, and proteins through blood and interstitial fluids to various organs. These unique and diverse features of HDL have encouraged its applications for the transport of therapeutics and diagnostic reagents in the last decade. In this review, we describe the heterogeneous characteristics and biological functions of HDL and highlight HDL mimetic approaches, including apolipoprotein mimetic peptides and reconstituted HDL nanoparticles. Given the potential of HDL as a nanocarrier delivering various therapeutic agents, we discuss the current representative studies of HDL mimetic nanotherapeutics for cardiovascular and neurodegenerative diseases and analyze the current challenges and future perspective. [ABSTRACT FROM AUTHOR]

The emergence and use of nanotechnologies in commercially available products, including nanotherapeutics, have necessitated the response of regulatory agencies to ensure that these products are safely employed. While bench scientists are at the forefront of nanoparticle development and design, many are unaware of the regulatory requirements necessary to transform their laboratory discoveries into marketable products. As bench scientists, we performed a 'thought experiment' using multifunctional mesoporous silica nanoparticles synthesized in our lab, which we considered as a combination product, to try to understand the steps necessary for pre-clinical approval from the Food and Drug Administration. This thought experiment illuminated challenges associated with nanoparticle risk assessment and regulation. [ABSTRACT FROM AUTHOR]

Nanotechnology provides multifunctional agents for in vivo use that increasingly blur the distinction between pharmaceuticals and medical devices. Realization of such therapeutic nanodevices requires multidisciplinary effort that is difficult for individual device developers to sustain, and identification of appropriate collaborations outside ones own field can itself be challenging. Further, as in vivo nanodevices become increasingly complex, their design will increasingly demand systems level thinking. System engineering tools such as object-oriented analysis, object-oriented design (OOA/D) and unified modeling language (UML) are applicable to nanodevices built from biological components, help logically manage the knowledge needed to design them, and help identify useful collaborative relationships for device designers. We demonstrate the utility of these systems engineering tools by reverse engineering an existing molecular device (the bacmid molecular cloning system) using them, and illustrate how object-oriented approaches identify fungible components (objects) in nanodevices in a way that facilitates design of families of related devices, rather than single inventions. We also explore tile utility of object-oriented approaches for design of another class of therapeutic nanodevices, vaccines. While they are useful for design of current nanodevices, the power of systems design tools for biomedical nanotechnology will become increasingly apparent as the complexity and sophistication of in vivo nanosystems increases. The nested, hierarchical nature of object-oriented approaches allows treatment of devices as objects in higher-order structures, and so will facilitate concatenation of multiple devices into higher-order, higher-function nanosystems. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments. Additionally, the difficulty of ensuring drugs effectively cross the natural blood–brain barrier (BBB) substantially reduces treatment efficiency. These conditions concomitantly limit the efficacy of standard chemotherapeutic agents available for GB. Indeed, there is an urgent need of a multifunctional drug vehicle system that has potential to transport anticancer drugs efficiently to the target and can successfully cross the BBB. In this review, we summarize some nanoparticle (NP)-based therapeutics attached to GB cells with antigens and membrane receptors for site-directed drug targeting. Such multicore drug delivery systems are potentially biodegradable, site-directed, nontoxic to normal cells and offer long-lasting therapeutic effects against brain cancer. These models could have better therapeutic potential for GB as well as efficient drug delivery reaching the tumor milieu. The goal of this article is to provide key considerations and a better understanding of the development of nanotherapeutics with good targetability and better tolerability in the fight against GB. [ABSTRACT FROM AUTHOR]

• CS-functionalized CUR-encapsulated polymeric NPs (CS-NPs) were produced. • CS-NPs had a diameter of 281 nm, good monodispersity, and negative-charged surface. • The conjugation of CS to NP surface endowed NPs with macrophage-targeted capacity. • Orally hydrogel embedding CS-NPs showed better therapeutic outcomes than non-targeted NPs. Orally targeted delivery of anti-inflammatory drugs to macrophages has attracted great attention for minimizing the symptoms of ulcerative colitis (UC). In this investigation, we encapsulated curcumin (CUR) into polymeric nanoparticles (NPs), and conjugated chondroitin sulfate (CS) to their surfaces. The resulting CS-NPs had an average diameter of 281 nm, monodisperse size distribution and negatively charged surface. Cell experiments indicated that these NPs showed excellent biocompatibility, and yielded significantly higher cell internalization efficiency in Raw 264.7 macrophages than their counterparts (carboxymethyl cellulose-functionalized CUR-encapsulated NPs, CUL-NPs). Moreover, CS-NPs exhibited a dramatically stronger capacity to inhibit the secretion of the major pro-inflammatory cytokines from lipopolysaccharide-stimulated macrophages compared with CUL-NPs. In vivo experiments revealed that oral administration of chitosan/alginate hydrogel embedding CS-NPs achieved better therapeutic outcomes against UC comparied with CUL-NPs. Collectively, our results demonstrated that CS-NP-embedded hydrogel held a great promise to be developed as a macrophage-targeted drug delivery system for UC treatment. [ABSTRACT FROM AUTHOR]