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Cancer immunotherapy has been demonstrated as a promising therapeutic strategy in clinic owing to its unique advantages. However, although more and more immunotherapeutic agents have been approved for clinical use to activate the immune system, they also could interfere with the homeostatic role of immune system at non-target sites after systemic administration, which may be associated with fatal side effects such as lifelong autoimmune diseases. Thus, it is desirable to develop local delivery systems that could be applied at the targeted sides and engineered to locally control the pharmacokinetics of various immunotherapeutics, including small molecules, macromolecules or even cells. Advancements in biomaterials, biotechnology, nanomedicine and engineering have facilitated the development of local delivery systems for enhanced cancer immunotherapy. This review will summarize the recent advances in developing different local delivery systems and discuss how these delivery systems could be designed to regulate the release behavior of different immunotherapeutics to sustainably stimulate the systemic immune system, effectively and safely inhibiting the cancer recurrence and metastasis. Furthermore, we will discuss how biomaterials-assisted local delivery systems would contribute to the development of cancer immunotherapy, together with their challenges and potential of clinical translation. Unlabelled Image [ABSTRACT FROM AUTHOR]

The world is grappling with the ongoing crisis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a global pandemic that continues to have a detrimental impact on public health and economies worldwide. The virus's relentless mutation has led to more transmissible, immune-evasive strains, thereby escalating the incidence of reinfection. This underscores the urgent need for highly effective and safe countermeasures against SARS-CoV-2 and its evolving variants. In the current context, nanomedicine presents an innovative and promising alternative to mitigate the impacts of this pandemic wave. It does so by harnessing the structural and functional properties at a nanoscale in a straightforward and adaptable manner. This review emphasizes the most recent progress in the development of nanovaccines, nanodecoys, and nanodisinfectants to tackle SARS-CoV-2 and its variants. Notably, the insights gained and strategies implemented in managing the ongoing pandemic may also offer invaluable guidance for the development of potent nanomedicines to combat future pandemics. [Display omitted] [ABSTRACT FROM AUTHOR]

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F. nucleatum -induced drug resistance, herein, we found that short-chain fatty acid butyrate can inhibit the growth, enrichment and adhesion of F. nucleatum in colorectal cancer tissues by downregulating the expression of adhesion-associated outer membrane proteins, including RadD, FomA, and FadA, to reduce the colonization and invasion of F. nucleatum and relieve the chemoresistance induced by F. nucleatum. Leveraging the killing effect of butyrate on F. nucleatum , sodium butyrate (NaBu) was encapsulated in liposomes or prepared as NaBu tablets with Eudragit S100 coating and administered by intravenous injection or oral administration, respectively. Interestingly, both intravenous administration of NaBu liposomes and oral delivery of NaBu tablets could effectively inhibit the proliferation of F. nucleatum and significantly improve the therapeutic efficacy of oxaliplatin in mice with subcutaneous colorectal tumors, orthotopic colorectal tumors and even spontaneously formed colorectal tumors. Thus, our work provides a simple but effective formulation of NaBu to relieve F. nucleatum -induced chemoresistance, exhibiting ideal clinical application prospects. [Display omitted] [ABSTRACT FROM AUTHOR]

As metal ions play important roles in the process of immunomodulation, immunotherapy based on metal ions has attracted tremendous interests in recent years. Here, we screened common metal ions and found that Mn2+ could enhance the immune function in vitro. A new type of nanovaccine is thus fabricated by a biomimetic approach using nanoscale coordination polymer formed by Mn2+ and 2-methylimidazole (2-MI) to encapsulate ovalbumin (OVA) protein, a model antigen, obtaining OVA@MM nanoparticles. Compared to free OVA, OVA@MM nanoparticles could more effectively induce the maturation of bone marrow-derived dendritic cells (BMDCs) and their subsequent antigen cross-presentation. The particles made of Mn2+ and 2-MI could activate immune-regulated signal pathways to enhance the immune functions of BMDCs. Such OVA@MM nanovaccine could not only provide prophylactic effect to inhibit the growth of B16-OVA tumor on immunized mice, but also significantly inhibit tumor growth in the mice with B16-OVA tumor combined with anti-programmed cell death protein 1 (anti-PD-1) antibody. Therefore, this nanovaccine platform based on Mn2+, 2-MI and antigen may provide a simple, effective and broadly applicable strategy to enhance adaptive immunity against cancer and other diseases. The nanoscale coordination polymers formed by manganese ions and 2-methylimidazole to encapsulate ovalbumin could enhance the maturation of BMDCs, promote the antigen cross-presentation, and trigger the specific antitumor immune response. [Display omitted] [ABSTRACT FROM AUTHOR]

Tumor hypoxia is confirmed to be associated with the formation of tumor immunosuppression, a general feature of solid tumors, and thus attenuates the effectiveness of various cancer therapies in clinic. We herein develop a tumor microenvironment (TME) modulating liposomal nanomedicine by encapsulating metformin with amphiphilic oxaliplatin prodrug constructed liposomes to potentiate cancer immunotherapy. While metformin could regulate metabolisms of tumor cells to reduce their oxygen consumption and relieve tumor hypoxia, oxaliplatin is a chemotherapy drug that induces immunogenic cell death (ICD). The obtained met-oxa(IV)-liposome upon intravenous injection effectively attenuates tumor hypoxia and induce ICD of cancer cells, thereby collectively suppresses the growth of murine colorectal tumors by eliciting potent antitumor immunity and reversing the immunosuppressive TME. As the result, the treatment with met-oxa(IV)-liposome effectively potentiates the immune checkpoint blockade (ICB) therapy against murine colorectal tumors. This liposomal nanomedicine is highlighted to be a TME modulating liposomal nanomedicine with high potency in suppressing tumor growth, particularly promising in synergizing with ICB therapy by boosting antitumor immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently identified regulated cell death pathway featured in iron prompted lipid peroxidation inside cells and found to be an effective approach to suppress tumor growth. Motived by the high efficacy of ferrous ions (Fe2+) in initiating intracellular lipid peroxidation via the Fenton reaction, this study herein prepares a pH-responsive Fe2+ delivery nanocarrier by coating calcium carbonate (CaCO 3) nanoparticles with a metal-polyphenol coordination polymer composed of gallic acid (GA) and Fe2+. Together with simultaneous encapsulation of succinic acid conjugated cisplatin prodrugs (Pt(IV)-SA) and Fe2+, the yielded nanoparticles, coined as PGFCaCO 3 , are synthesized and exhibit uniform hollow structure. After PEGylation, the resulted PGFCaCO 3 -PEG shows increased physiological stability and pH-dependent decomposition, drug release and catalytic capability in initiating lipid peroxidation. After being endocytosed, PGFCaCO 3 -PEG effectively promoted intracellular generation of cytotoxic reactive oxygen species including lipid peroxide, thereby exhibited superior inhibition effect towards both murine 4T1 and CT26 cancer cells over Pt(IV)-SA and GFCaCO 3 -PEG. As a result, treatment with systemic administration of PGFCaCO 3 -PEG effectively suppressed 4T1 tumor growth via combined Fe2+ initiated ferroptosis and Pt(IV)-SA mediated chemotherapy. This work highlights that intracellular delivery of Fe2+ is a robust approach to enhance tumor chemotherapy by inducing ferroptosis. PGFCaCO 3 -PEG prepared via the surface protected etching process is employed to enable tumor targeted delivery of cisplatin prodrug Pt(IV)-SA and Fe2+. Upon uptake by tumor cells, the released Pt(IV)-SA is reduced to its toxic species of cisplatin to suppress cancer cells via the chemotherapy. Subsequently, the released Fe2+ converts endogenous H 2 O 2 into cytotoxic ·OH via the Fenton reaction to promote intracellular lipid peroxidation, thereby eliciting ferroptosis of cancer cells. As a result, PGFCaCO 3 -PEG could collectively suppress tumor cell growth via the chemotherapy and ferroptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Development of multifacted phototheranostics with bright fluorescence and absorbance in the second near infrared (NIR-II) window is very appealing for precise cancer diagnosis and treatment, but still challenging nowadays. Herein, we synthesize a hydrophobic annularly fused azaBODIPY (termed as HBP) molecule with sharp NIR absorbance peaked at 878 nm and bright NIR-II fluorescence. With Pluronic F127 as the surfactant and hydrophobic paclitaxel (PTX) as the spacer, such HBP molecule would self-assemble to form surfactant-stripped HBP/PTX micelles with absorption peak red-shifted to 1012 nm and intrinsic NIR-II fluorescence negligibly disturbed. We found that such HBP/PTX micelles can be utilized as a bimodal NIR-II nano-probe to enable real-time tracking of lymph nodes and tumors under an NIR-II fluorescence imaging system, as well as clear visualization of tumor microvasculatures under an NIR-II photoacoustic imaging system. Furthermore, together with 1064 nm laser exposure, such HBP/PTX micelles would synergistically suppress the growth of tumors grown on the mice upon tumor accumulation. This work highlights the concise preparation of a type of all-in-one NIR-II phototheranostics from the newly synthesized HBP molecules, thereby enables NIR-II fluorescence/photoacoustic bimodal imaging guided synergistic cancer treatment via the NIR-II laser boosted photothermal therapy and chemotherapy. An all-in-one NIR-II phototheranostics prepared from aza-BODIPY molecules via the J-aggregates formation process is utilized for simultaneous NIR-II fluorescence & PA bimodal imaging guided synergistic NIR-II boosted PTT and chemotherapy. Unlabelled Image • HBP/PTX micelles exhibit newly emerged NIR-II absorbance owing to J-aggregates formation. • HBP/PTX micelles enable simultaneous NIR-II fluorescence and photoacoustic imaging. • HBP/PTX micelles contribute to effective cancer treatment via NIR-II laser boosted PTT and chemotherapy [ABSTRACT FROM AUTHOR]

Cancer local physical therapy (PT) by using heat, cold, electrical stimulation, irradiation or ultrasound to treat tumor is accepted as alternative choice for cancer patients. However, local recurrence and metastasis after such treatments remains to be the major cause of treatment failure and mortality. Therefore, it is necessary to develop a therapeutic strategy to inhibit local recurrence and metastasis. Inspired by the excellent inflammatory targeting ability of platelets, here we expect that the monoclonal antibody against programmed-death ligand 1 (aPDL1) engineered platelets could inhibit tumor local recurrence effectively, by facilitating transport of anti-PD-L1 antibodies to the ablated area with residue tumors. Using triple-negative breast carcinomas (4T1) bearing mouse model, we proved that antibody-coupled platelets could effectively target incompletely ablated tumor with thermal ablation (TA). We found the release of anti-PD-L1 can be triggered upon the platelets activation, together with many pro-inflammatory cytokines. The release of anti-PD-L1 is likely due to the dissociation of platelets upon the activation. Our findings approved that our platelet-based platform could facilitate the delivery of immune checkpoint antibody to tumor residues and remarkably prevent tumor recurrence after ablation. Moreover, this platelet-based delivery strategy may be extended to the targeted delivery of therapeutics post other types of local therapies including photodynamic therapy, high-intensity-focused-ultrasound ablation therapy, and even radiotherapy. Unlabelled Image [ABSTRACT FROM AUTHOR]

The abnormal tumor microenvironment (TME) featured with hypoxia, acidosis, dense extracellular matrix and increased tumor interstitial fluid pressure is closely related with the resistance of tumors to various therapies. Herein, a unique type of biocompatible nanoscale delivery system is fabricated by utilizing a chemotherapeutic drug, paclitaxel (PTX), to induce co-assembly of catalase and human serum albumin (HSA), the latter of which is pre-modified with chlorine e6 (Ce6), forming smart multifunctional HSA-Ce6-Cat–PTX nanoparticles via a rather simple one-step method. Upon intravenous injection, HSA-Ce6-Cat–PTX nanoparticles show high tumor accumulation and efficient intra-tumoral diffusion, likely owning to their changeable sizes that can maintain large initial sizes (~ 100 nm) during blood circulation and transform into small protein-drug complexes (< 20 nm) within the tumor. Meanwhile, catalase within those nanoparticles could trigger decomposition of endogenic TME H 2 O 2 to generate oxygen in-situ so as to relieve tumor hypoxia. This effect together with PTX-induced intra-tumoral perfusion enhancement is able to dramatically modulate TME to favor the anti-tumor effect in the combined photodynamic/chemotherapy with HSA-Ce6-Cat–PTX. Thus, our work presents a simple drug-induced self-assembly strategy to fabricate enzyme-loaded therapeutic albumin nanoparticles for synergistic cancer combination therapy. [ABSTRACT FROM AUTHOR]

cRGD-directed, NIR-responsive and robust AuNR/PEG–PCL hybrid nanoparticles (cRGD-HNs) were designed and developed for targeted chemotherapy of human glioma xenografts in mice. As expected, cRGD-HNs had excellent colloidal stability. The in vitro release studies showed that drug release from DOX-loaded cRGD-HNs (cRGD-HN-DOX) was minimal under physiological conditions but markedly accelerated upon NIR irradiation at a low power density of 0.2 W/cm 2 , due to photothermally induced phase transition of PCL regime. MTT assays showed that the antitumor activity of cRGD-HN-DOX in α v β 3 integrin over-expressed human glioblastoma U87MG cells was greatly boosted by mild NIR irradiation, which was significantly more potent than non-targeting HN-DOX counterpart under otherwise the same conditions and was comparable or superior to free DOX, supporting receptor-mediated endocytosis mechanism. The in vivo pharmacokinetics studies showed that cRGD-HN-DOX had much longer circulation time than free DOX. The in vivo imaging and biodistribution studies revealed that cRGD-HN-DOX could actively target human U87MG glioma xenograft in nude mice. The therapeutic studies in human U87MG glioma xenografts exhibited that cRGD-HN-DOX in combination with NIR irradiation completely inhibited tumor growth and possessed much lower side effects than free DOX. The Kaplan–Meier survival curves showed that all mice treated with cRGD-HN-DOX plus NIR irradiation survived over an experimental period of 48 days while control groups treated with PBS, cRGD-HN-DOX, cRGD-HNs with NIR irradiation, free DOX, or HN-DOX with NIR irradiation (non-targeting control) had short life spans of 15–40 days. Ligand-directed AuNR/PEG–PCL hybrid nanoparticles with evident tumor-targetability as well as superior spatiotemporal and rate control over drug release have emerged as an appealing platform for cancer chemotherapy in vivo . [ABSTRACT FROM AUTHOR]