A single-step plasma method for rapid production of 2D, ferromagnetic, surface vacancy-engineered MoO3-xnanomaterials, for photothermal ablation of cancer.

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 MoO3-xis 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 MoO3-xnanomaterials are stable against further oxidation even under prolonged atmospheric exposure.In vitroexperiments confirm that they have ideal efficacy for photothermal ablation of human and murine melanoma cancer at relatively lower dose. Duringin vivoPTT 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.

Inflammatory-stimuli-responsive turn-on NIR fluorogenic theranostic prodrug: adjuvant delivery of diclofenac and hydrogen sulfide attenuates acute inflammatory disorders.

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 (H2S). 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 H2O2 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 H2S was investigated in HeLa cells using the H2S-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.

Biocompatible arabinogalactan-chitosan scaffolds for photothermal pharmacology in wound healing and tissue regeneration.

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.

Bioactive Polymeric Nanoparticles of Moringa oleifera Induced Phyto-Photothermal Sensitization for the Enhanced Therapy of Retinoblastoma.

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.

Bio-nanoconjugates of lithocholic acid/IR 780 for ROS-mediated apoptosis and optoacoustic imaging applications in breast cancer.

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.

Multifunctional Polymeric Nanoparticles for Chemo/Phototheranostics of Retinoblastoma.

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.

Investigation of ROS generating capacity of curcumin-loaded liposomes and its in vitro cytotoxicity on MCF-7 cell lines using photodynamic therapy.

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.

Nutraceutical prospects of Houttuynia cordata against the infectious viruses.

The novel enveloped ß-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.

Polyphenolic-Rich Compounds From Dillenia pentagyna (Roxb.) Attenuates the Doxorubicin-Induced Cardiotoxicity: A High-Frequency Ultrasonography Assisted Approach.

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.