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Myocardial infarction is a condition where the heart muscle is damaged due to clogged coronary arteries. There are limited treatment options for treating myocardial infarction. Microneedle patches have recently become popular as a possibly viable therapy for myocardial. By adhering to the surface of the heart, these microneedle patches provide mechanical support, regenerative medicines, or cells directly to the injured tissue allowing for targeted treatment. These microneedle patches resolve the drawbacks of systemic therapy by facilitating targeted administration and integration with the goal of restoring damaged heart function. Recent advances in fabrication methods and current perspectives on the therapeutic advantages of cardiac microneedles patches used in the treatment of myocardial infarction are summarized in this review. Although the data is less in this area this review provides an avenue for the formulation scientist working in biomedical science to develop such microneedle patches for clinical applications in cardiology., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: We agreed with the journal policy and provided our consent for the publication. Competing interest: The authors declare that they have no conflict of interest., (© 2025. Controlled Release Society.)

The surge in spinal cord injuries (SCI) attracted many neurobiologists to explore the underlying complex pathophysiology and to offer better therapeutic outcomes. The multimodal approaches to therapy in SCI have proven to be effective but to a limited extent. The clinical basics involve invasive procedures and limited therapeutic interventions, and most preclinical studies and formulations are yet to be translated due to numerous factors. In recent years, photobiomodulation therapy (PBMT) has found many applications in various medical fields. In most PBMT, studies on SCI have employed laser sources in experimental animal models as a non-invasive source. PBMT has been applied in numerous facets of SCI pathophysiology, especially attenuation of neuroinflammatory cascades, enhanced neuronal regeneration, reduced apoptosis and gliosis, and increased behavioral recovery within a short span. Although PBMT is specific in modulating mitochondrial bioenergetics, innumerous molecular pathways such as JAK-STAT, PI3K-AKT, NF-κB, MAPK, JNK/TLR/MYD88, ERK/CREB, TGF-β/SMAD, GSK3β-AKT-β-catenin, and AMPK/PGC-1α/TFAM signaling pathways have been or are yet to be exploited. PMBT has been effective not only in cell-specific actions in SCI such as astrocyte activation or microglial polarization or alterations in neuronal pathology but also modulated overall pathobiology in SCI animals such as rapid behavioral recovery. The goal of this review is to summarize research that has used PBMT for various models of SCI in different animals, including clarifying its mechanisms and prospective molecular pathways that may be utilized for better therapeutic outcomes., Competing Interests: Declarations. Ethical Approval: This declaration is not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acne Vulgaris or Acne is a multifactorial bacterial infection caused by Propionibacterium acne, leading to inflammation and decreased quality of life, especially in adolescence. Currently, antibiotics and retinoids are preferred for treating acne. However, their continuous usage may lead to anti-microbial resistance and other side effects. Therefore, research on developing effective strategies to reduce antimicrobial resistance and improve acne healing is ongoing. The current work reports the synthesis and evaluation of near-infrared light-absorbing copper sulfide (CuS) nanoparticles loaded with a biomolecule, Glycyrrhizin (Ga). The photothermal efficacy studies, and in-vitro and in-vivo experiments indicated that the Ga-CuS NPs generated localized hyperthermia in acne-causing bacteria, leading to their complete growth inhibition. The results indicated that the Ga-Cus NPs possess excellent antibacterial and anti-inflammatory properties in the acne and inflammatory models. This could be from the synergistic effect of CuS NPs mediated mild Photothermal effect and inherent pharmacological properties of Ga. Further detailed studies of the formulations can pave the way for application in cosmetic clinics for the effective and minimally invasive management of Acne-like conditions., (© 2024. Controlled Release Society.)

Prolonged use of very commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with undesired side effects, including gastrointestinal ulcers due to the non-selective inhibition of cyclooxygenases. We describe the development of an inflammatory-stimuli-responsive turn-on fluorogenic theranostic prodrug DCF-HS for adjuvant drug delivery. Upon activation by reactive oxygen species (ROS), the prodrug releases diclofenac DCF (active drug) and the NIR fluorophore DCI-NH2 along with carbonyl sulfide (COS). The second activation of COS by the enzyme carbonic anhydrase (CA) generates hydrogen sulfide (H 2 S). The prodrug was conveniently synthesized using multi-step organic synthesis. The UV-Vis and fluorescence studies revealed the selective reactivity of DCF-HS towards ROS such as H 2 O 2 in the aqueous phase and the desired uncaging of the drug DCF with turn-on NIR fluorescent reporter under physiological conditions. Furthermore, the release of fluorophore DCI-NH2 and drug DCF was confirmed using the reverse phase HPLC method. Compatibility of prodrug activation was studied next in the cellular medium. The prodrug DCF-HS was non-toxic in a representative cancer cell line (HeLa) and a macrophage cell line (RAW 264.7) up to 100 μM concentration, indicating its biocompatibility. The intracellular ROS-mediated activation of the prodrug with the release of NIR dye DCI-NH2 and H 2 S was investigated in HeLa cells using the H 2 S-selective probe WSP2. The anti-inflammatory activity of the active drug DCF from the prodrug DCF-HS was studied in the lipopolysaccharide (LPS)-induced macrophage cell line and compared to that of the parent drug DCF using western blot analysis and it was found that the active drug resulted in pronounced inhibition of COX-2 in a dose-dependent manner. Finally, the anti-inflammatory potential of the prodrug and the turn-on fluorescence were validated in the inflammation-induced Wister rat models.

Delayed wound healing is often caused by bacterial infections and persistent inflammation. Multifunctional materials with anti-bacterial, anti-inflammatory, and hemostatic properties are crucial for accelerated wound healing. In this study, we report a biomacromolecule-based scaffold (ArCh) by uniquely combining arabinogalactan (Ar) and chitosan (Ch) using a Schiff-based reaction. Further, the optimized ArCh scaffolds were loaded with Glycyrrhizin (GA: anti-inflammatory molecule) conjugated NIR light-absorbing Copper sulfide (CuS) nanoparticles. The resultant GACuS ArCh scaffolds were characterized for different wound healing parameters in in-vitro and in-vivo models. Our results indicated that GACuS ArCh scaffolds showed excellent swelling, biodegradation, and biocompatibility in vitro. Further results obtained indicated that GACuS ArCh scaffolds demonstrated mild hyperthermia and enhanced hemostatic, anti-oxidant, anti-bacterial, and wound-healing effects when exposed to NIR light. The scaffolds, upon further validation, may be beneficial in accelerating wound healing and tissue regeneration response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A rapid, clean plasma-chemical technique is demonstrated here, for cost-effective, synthesis of surface vacancy engineered, 2D, molybdenum-oxide nanomaterials, during a one-step, integrated synthesis-hydrogenation process for biomedical applications. A laminar plasma beam populated with O and H radicals impinges on a molybdenum target, out of which molybdenum-oxide nanomaterials are very rapidly generated with controlled surface O vacancies. 2D, dark-blue coloured, nano-flake/ribbon like MoO 3- x is produced maximum up to 194 g h -1 , the core of which still remains as stoichiometric molybdenum-oxide. These nanomaterials can get heated-up by absorbing energy from a near-infrared (NIR) laser, which enable them as photothermal therapy (PTT) candidate material for the invasive precision therapy of cancer. The surface defects endows the products with robust ferromagnetism at room temperature conditions (maximum saturation-magnetization: 6.58 emu g -1 ), which is order of magnitude stronger than most other vacancy engineered nanomaterials. These nanometric metal-oxides are observed to be perfectly compatible in animal physiological environment and easily dispersed in an aqueous solution even without any pre-treatment. The MoO 3- x nanomaterials are stable against further oxidation even under prolonged atmospheric exposure. In vitro experiments confirm that they have ideal efficacy for photothermal ablation of human and murine melanoma cancer at relatively lower dose. During in vivo PTT treatments, they may be manipulated with a simple external magnetic field for targeted delivery at the malignant tumours. It is demonstrated that commensurate to the neutralization of the malignant cells, the nanomaterials themselves get self-degraded, which should get easily excreted out of the body., (© 2023 IOP Publishing Ltd.)

Treatment of retinoblastoma is limited due to its delayed detection and inaccesbility of drugs to reach the retina crossing the blood-retinal barrier. With the advancements in nanotechnology, photothermal therapy (PTT) employing plasmonic nanomaterials and/or NIR dyes have emerged as an affordable alternative owing to the spatial control that is offered by the modality leading to localized and enhanced therapeutic efficacy with minimal invasiveness. However, the modality is limited in its clinical application owing to the increased heat shock resistance of the tumor cells in response to the heat that is generated via PTT. Hence, in this study, we explore the role of novel biomolecular fraction of Moringa oleifera (DFM) encapsulated within a polymeric nanosystem, for its anti-heat shock protein (HSP) activity. The MO extract was co-encapsulated with NIR sensitizing dye, IR820 into a biodegradable polycaprolactone (PCL) nano-delivery system (PMIR NPs). The photothermal transduction efficacy of PMIR NPs was validated in vitro against retinoblastoma cell lines. The inherent fluorescence of DFM was utilized to evaluate the cellular internalization of the PMIR NPs using fluorescence microscopy and flow cytometry. The overall oxidative protein damage and downregulation of HSP70 expression upon treatment with PMIR NPs and NIR laser irradiation was evaluated using densiometric protein analysis and Western blotting. Overall, the PMIR NPs exhibited excellent anti-cancer activity when combined with PTT with downregulated HSP70 expression against retinoblastoma cells.

A new lithocholic acid/IR 780 conjugate (LIC) was designed and synthesized for theranostic applications in triple-negative breast cancer. Lithocholic acid is an antitumor biomacromolecule and acts via multiple molecular targets. IR 780 iodide is a fluorescent NIR organic dye researched as a photothermal agent in cancer therapy. A combined conjugate, LIC can have wide applications as a Photothermal/chemotherapeutic and imaging agent in cancer therapy. LIC was characterized and evaluated for its photothermal cytotoxic effect in breast cancer cell lines. Further, to improve the bioavailability of the LIC, a polymeric (PLGA) nanosystem was developed and characterized. The resultant lithocholic acid/IR 780 polymeric nanoconjugates (LIPNCs) were well taken up by the cells and are evident by the inherent red fluorescence of LIC. The LIPNCs also exhibited commendable heat generation when exposed to NIR light (808 nm). The in-vitro anti-cancer studies of LIPNCs also revealed a significant NIR light-based photothermal efficacy (cytotoxic dose 0.75 μM) when compared to the free conjugate (LIC) or the parent moieties. Further cell-based fluorescent and molecular assays showed that LIPNCs induced ROS-mediated apoptotic cell death concurrently being physiologically biocompatible. In-vitro photoacoustic imaging of the LICs exhibited signals comparable to free IR780 dye. Future in vivo studies with LIPNCs or LIC may prove beneficial for developing a promising translational system for its wide application in image-guided cancer theranostics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of interest There are no conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is highly efficient in eradicating targetlesions by using photosensitizers (PS) triggered by external light energy. Nanotechnology may help increase the solubility and effective delivery of PS towards improving its efficacy. Curcumin (Cur) was used as a natural PS for PDT in the present work. Briefly, curcumin was encapsulated in liposomes (LPs) using the thin film hydration method and optimized using the QbD approach through the Box-Behnken Design (BBD) to optimize the responses like entrapment efficiency and drug loading with a smaller vesicle size. The in vitro release studies performed using a dialysis bag (MWCO 12 KDa) suggested a sustained release of the Cur over 72 h in pH 7.4 PBS following the Weibull drug release kinetics. In addition, the ROS generating capabilities upon application of blue light (460 nm) and resulting cytotoxicity were evaluated in MCF-7 cell lines. The Cur-loaded liposome exhibited significant ROS generation and cytotoxicity to the cancer cells than free curcumin. Thus, the Cur-loaded liposomes could be used to treat breast cancer with photodynamic therapy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The novel enveloped β-coronavirus SARS-CoV-2 (COVID-19) has offered a surprising health challenge all over the world. It develops severe pneumonia leading to acute respiratory distress syndrome (ARDS). Like SARS-COV-2, other encapsulated viruses like HIV, HSV, and influenza have also offered a similar challenge in the past. In this regard, many antiviral drugs are being explored with varying degrees of success to combat the associated pathological conditions. Therefore, upon scientific validation & development, these antiviral phytochemicals can attain a futuristic nutraceutical prospect in managing different encapsulated viruses. Houttuynia cordata (HC) is widely reported for activities such as antioxidant, anti-inflammatory, and antiviral properties. The major antiviral bioactive components of HC include essential oils (methyl n-nonyl ketone, lauryl aldehyde, capryl aldehyde), flavonoids (quercetin, rutin, hyperin, quercitrin, isoquercitrin), and alkaloids (norcepharadione B) & polysaccharides. HC can further be explored as a potential nutraceutical agent in the therapy of encapsulated viruses like HIV, HSV, and influenza. The review listed various conventional and green technologies that are being employed to extract potent phytochemicals with diverse activities from the HC. It was indicated that HC also inhibited molecular targets like 3C-like protease (3CLPRO) and RNA-dependent RNA polymerase (RdRp) of COVID-19 by blocking viral RNA synthesis and replication. Antioxidant and hepatoprotective effects of HC have been evident in impeding complications from marketed drugs during antiviral therapies. The use of HC as a nutraceutical is localized within some parts of Southeast Asia. Further technological advances can establish it as a nutraceutical-based functional food against pathogenic enveloped viruses like COVID 19., Competing Interests: The authors declare no conflicts of interest., (© 2022 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Ervatamia coronaria, a popular garden plant in India and some other parts of the world is known traditionally for its anti-inflammatory and anti-cancer properties. The molecular bases of these functions remain poorly understood., Aim of the Study: Efficacies of the existing therapies for colorectal cancer (CRC) are limited by their life-threatening side effects and unaffordability. Therefore, identifying a safer, efficient, and affordable therapeutic is urgent. We studied the anti-CRC activity of an alkaloid-rich fraction of E. coronaria leaf extracts (AFE) and associated underlying mechanism., Materials and Methods: Activity guided solvant fractionation was adopted to identify the activity in AFE. Different cell lines, and tumor grown in syngeneic mice were used to understand the anti-CRC effect. Methodologies such as LCMS, MTT, RT-qPCR, immunoblot, immunohistochemistry were employed to understand the molecular basis of its activity., Results: We showed that AFE, which carries about six major compounds, is highly toxic to colorectal cancer (CRC) cells. AFE induced cell cycle arrest at G1 phase and p21 and p27 genes, while those of CDK2, CDK-4, cyclin-D, and cyclin-E genes were downregulated in HCT116 cells. It predominantly induced apoptosis in HCT116p53+/+ cells while the HCT116p53-/- cells under the same treatment condition died by autophagy. Notably, AFE induced upregulation of AMPK phosphorylation, and inhibition of both of the mTOR complexes as indicated by inhibition of phosphorylation of S6K1, 4EBP1, and AKT. Furthermore, AFE inhibited mTOR-driven conversion of cells from reversible cell cycle arrest to senescence (geroconversion) as well as ERK activity. AFE activity was independent of ROS produced, and did not primarily target the cellular DNA or cytoskeleton. AFE also efficiently regressed CT26-derived solid tumor in Balb/c mice acting alone or in synergy with 5FU through inducing autophagy as a major mechanism of action as indicated by upregulation of Beclin 1 and phospho-AMPK, and inhibition of phospho-S6K1 levels in the tumor tissue lysates., Conclusion: AFE induced CRC death through activation of both apoptotic and autophagy pathways without affecting the normal cells. This study provided a logical basis for consideration of AFE in future therapy regimen to overcome the limitations associated with existing anti-CRC chemotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Retinoblastoma (Rb) is the most critical and severe intraocular malignancy occurring in children. The clinical management of retinoblastoma is still challenging due to failure in early detection and control despite the advancements in medical strategies. Early-stage Rb tumors do not occupy major visual fields, so chemo/photothermal therapy (PTT) with biocompatible materials can be a practical approach. Herein, we report multifunctional polymeric nanoparticles (PNPs) entrapped with an FDA-approved anticancer drug, Palbociclib (PCB), and a near-infrared dye, IR820 (IR), as chemo/photothermal agents. These PCB/IR PNPs were evaluated for the combinational effect in the retinoblastoma cell line. Further, the in vivo photoacoustic imaging efficacy and acute toxicity profile of the PNPs were studied in a mice model. The results indicated that the PCB/IR PNPs exhibited a significant cytotoxic effect (86.5 ± 2.3%) in Y79 cell lines than the respective control groups upon exposure to NIR light. Qualitative and quantitative analyses indicated that PCB/IR PNPs with NIR light induction resulted in DNA damage followed by apoptosis. PCB/IR PNPs, when tested in vivo, showed optimal photoacoustic signals. Thus, the combination of PCB and PTT can emerge as a translational modality for retinoblastoma therapy.

Cardiovascular complications are the foremost concern in patients undergoing anticancer therapy . There is an unmet need to address the problems arising from the drug-induced toxicity for the long-term benefit of the patients undergoing chemotherapy. Alternative medicines are gaining their prosperity in addressing the various drug-induced organ toxicity. Dillenia pentagyna Roxb (DP) is an ethnomedicinal plant rich in flavonoids and phenolic contents. In India & Nepal, DP is a common ingredient of traditional medicines used to treat multiple ailments like inflammation, cancer, and diabetes. However, its protective role against doxorubicin (Dox) induced cardiotoxicity remains unexplored. Herein, we investigated the potential effects of various extracts/fractions obtained from the DP's bark against Dox-induced cardiotoxicity, both in-vitro and in-vivo . The anti-oxidant content of the extracts/fractions was evaluated by using DPPH, ABTS and FRAP chemical assays. The results indicated that the hydroalcoholic (HA) extract of DP has intense anti-oxidant potential. Further fractionation of DP revealed that the phenolic-rich fraction (F1) has a high anti-oxidant potential. The protective effect of extract/fraction was also investigated in the H9c2 cell line following the Dox-induced cardiotoxicity model. We observed that the pre-treatment of extract/fraction in cardiomyocytes had exhibited increased cell viability. Fluorescence-based chemical assays indicated a decreased ROS levels in the treated groups in comparison to the Dox control group. The effect of DP was evaluated further in balb/c mice by the Dox-induced cardiotoxicity model. Non-invasive techniques like high-frequency ultrasonography and electrocardiogram revealed that the mice pre-treated with DP had improved cardiac functionality (left ventricular ejection fraction and stroke volume) and normalized the electrocardiograms compared to the Dox control group. Further, biochemical analysis with the cardiac tissues revealed that the cytoprotective proteins like HO-1, SOD-2, and Nrf-2 were elevated in the DP treated groups compared to the Dox control group. Overall, our results suggested that the bioactive extract/fractions of DP helped alleviate the Dox-induced cardiotoxicity. LC-QTOF-ESI-MS analysis of DP and F1 indicated that polyphenolic anti-oxidant compounds like gallic acid, syringic acid, and sinapic acid could be responsible for the potent -cardioprotective effect. Future understanding of the pharmacokinetics and pharmacodynamic parameters can help translate from the bench to the bedside., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tene, Kalyan Kumar, Basveshwar, Eswara Rao, Jagadeesh Kumar, kumar, Pemmaraju, Murty, Gogoi and Naidu.)

Light-responsive nanoliposomes are being reported to induce cancer cell death through heat and reactive oxygen species (ROS). Nanoliposomes (CIR NLPs) encapsulating a near-infrared (NIR) light-sensitive dye, IR780, and a bioactive chlorophyll-rich fraction of Anthocephalus cadamba (CfAc) were synthesized and characterized. These CIR NLPs, when activated by NIR light, displayed localized synergistic cancer cell death under in vitro and in vivo conditions. We demonstrated a NIR light-mediated release of CfAc in cancer cells. The bioactive CfAc was selective in causing ROS generation (leading to autophagic cell death) in cancer cells, while normal healthy cells were unaffected. An increase in the intracellular ROS leading to enhanced lipidation of microtubule-associated protein light chain 3 (LC3-II) was observed only in cancer cells, while normal cells showed no increase in either ROS or LC3-II. In vivo analysis of CIR NLPs in an orthotopic mouse model showed better anti-tumorigenic potential through a combined effect (i.e. via heat and CfAc). We reported for the first time induction of selective and localized, bioactive phyto fraction-mediated autophagic cancer cell death through an NIR light trigger. The synergistic activation of ROS-mediated autophagy by light-triggered nanoliposomes can be a useful strategy for enhancing the anticancer potential of combinational therapies.

We report the synthesis of a biodegradable liposome gold nanoparticles for curcumin (Au-Lipos Cur NPs) delivery. This entrapped curcumin served as an in situ adjuvant for photothermal therapy. Curcumin was loaded in Au-Lipos NPs with an encapsulation efficiency of ∼70%. The gold coating enabled the NPs to specifically absorb NIR light (780nm) by virtue of Surface Plasmon Resonance (SPR) and this light energy was converted to heat. The generated heat destabilized the liposomal core enhancing the release of encapsulated curcumin. Photothermal transduction efficacy of Au-Lipos NPs (loaded with curcumin) showed a significant temperature rise upon laser irradiation causing irreversible cellular damage. In vitro photothermal effect and intracellular uptake was evaluated in B16 F10 (melanoma) cell line. Au-Lipos Cur NPs showed significantly enhanced uptake when compared with free curcumin. Enhancement in cancer cell cytotoxicity was observed in Au-Lipos Cur NPs treated group upon laser irradiation owing to curcumin. Our findings indicate that curcumin could serve as a potential in situ adjuvant for photothermal therapy of melanoma., (Copyright © 2017 Elsevier B.V. All rights reserved.)