Sodium Niobate Nanowires Embedded PVA-Hydrogel-Based Triboelectric Nanogenerator for Versatile Energy Harvesting and Self-Powered CO Gas Sensor.

The surging demand for sustainable energy solutions and adaptable electronic devices has led to the exploration of alternative and advanced power sources. Triboelectric Nanogenerators (TENGs) stand out as a promising technology for efficient energy harvesting, but research on fully flexible and environmental friendly TENGs still remain limited. In this study, an innovative approach is introduced utilizing an ionic-solution modified conductive hydrogel embedded with piezoelectric sodium niobate nanowires-based Triboelectric Nanogenerator (NW-TENG), offering intrinsic advantages to healthcare and wearable devices. The synthesized NW-TENG, with a 12.5 cm2 surface area, achieves peak output performance, producing ≈840 V of voltage and 2.3 µC of charge transfer, respectively. The rectified energy powers up 30 LEDs and a stopwatch; while the NW-TENG efficiently charges capacitors from 1µF to 100 µF, reaching 1 V within 4 to 65 s at 6 Hz. Integration with prototype carbon monoxide (CO) gas sensor transform the device into a self-powered gas sensory technology. This study provides a comprehensive understanding of nanowire effects on TENG performance, offering insights for designing highly flexible and environmentally friendly TENGs, and extending applications to portable self-powered gas sensors and wearable devices.

Excellent Adsorption of Lead (II) and Chromium (VI) from Water Using Zwitterions (-NH3+ and -COO-) Functionalized Nano Lanthanum Oxide: Kinetic, Isotherm, Thermodynamic, and Surface Mechanism.

Zwitterion amino acid l-cysteine functionalized lanthanum oxide nanoparticles (l-Cyst-La2O3 NPs) have been synthesized for the first time with lanthanum acetate as the precursor, NH4OH as the base, and l-cysteine as the in situ functionalized mediator. The typical size of l-Cyst-La2O3 NPs was obtained in the range of 15-20 nm from the TEM technique. A cytotoxicity test of l-Cyst-La2O3 NPs was performed in Raw 264.7 cell lines, which were shown to be highly biocompatible. The point zero charge pH (pHPZC) of bare and l-Cyst functionalized La2O3 NPs was obtained at pH 6 and 2. The maximum uptake capacities of l-Cyst-La2O3 NPs at temperatures 25-45 °C were obtained as 137-282 mg/g for Pb2+ and 186-256 mg/g for Cr6+. All of these values are much higher than those reported in the literature with other nanomaterials. The presence of -SH, -NH2, and -COOH functional groups in zwitterion l-cysteine provides multiple binding sites leading to the high adsorption of Pb2+ and Cr6+. Five-cycle desorption studies were successfully performed to regenerate the spent l-Cyst-La2O3 NPs.

Robotically facilitated parafasicular microsurgery to a brain arteriovenous malformation in a paediatric patient.

PURPOSE: We report what we believe is the first application of robotically constrained image-guided surgery to approach a fistulous micro-arteriovenous malformation in a highly eloquent location. Drawing on institutional experience with a supervisory-control robotic system, a series of steps were devised to deliver a tubular retractor system to a deeply situated micro-arteriovenous malformation. The surgical footprint of this procedure was minimised along with the neurological morbidity. We hope that our contribution will be of assistance to others in integrating such systems given a similar clinical problem. CLINICAL PRESENTATION: A right-handed 9-year old girl presented to her local emergency department after a sudden onset of severe headache accompanied by vomiting. An intracranial haemorrhage centred in the right centrum semiovale with intraventricular extension was evident and she was transferred urgently to the regional paediatric neurosurgical centre, where an external ventricular drain (EVD) was sited. A digital subtraction angiogram demonstrated a small right hemispheric arteriovenous shunt irrigated by peripheral branches of the middle cerebral artery & a robotically facilitated parafasicular microsurgical approach was performed to disconnect the arteriovenous malformation. CONCLUSION: We describe the successful microsurgical in-situ disconnection of a deeply-situated, fistulous micro-AVM via a port system itself delivered directly to the target with a supervisory-control robotic system. This minimised the surgical disturbance along a relatively long white matter trajectory and demonstrates the feasibility of this approach for deeply located arteriovenous fistulae or fistulous AVMs.

Integrated Microbiota and Metabolite Changes following Rice Bran Intake during Murine Inflammatory Colitis-Associated Colon Cancer and in Colorectal Cancer Survivors.

Dietary rice bran-mediated inhibition of colon carcinogenesis was demonstrated previously for carcinogen-induced rodent models via multiple anti-cancer mechanisms. This study investigated the role of dietary rice bran-mediated changes to fecal microbiota and metabolites over the time course of colon carcinogenesis and compared murine fecal metabolites to human stool metabolic profiles following rice bran consumption by colorectal cancer survivors (NCT01929122). Forty adult male BALB/c mice were subjected to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colon carcinogenesis and randomized to control AIN93M (n = 20) or diets containing 10% w/w heat-stabilized rice bran (n = 20). Feces were serially collected for 16S rRNA amplicon sequencing and non-targeted metabolomics. Fecal microbiota richness and diversity was increased in mice and humans with dietary rice bran treatment. Key drivers of differential bacterial abundances from rice bran intake in mice included Akkermansia, Lactococcus, Lachnospiraceae, and Eubacterium xylanophilum. Murine fecal metabolomics revealed 592 biochemical identities with notable changes to fatty acids, phenolics, and vitamins. Monoacylglycerols, dihydroferulate, 2-hydroxyhippurate (salicylurate), ferulic acid 4-sulfate, and vitamin B6 and E isomers significantly differed between rice bran- and control-fed mice. The kinetics of murine metabolic changes by the host and gut microbiome following rice bran consumption complemented changes observed in humans for apigenin, N-acetylhistamine, and ethylmalonate in feces. Increased enterolactone abundance is a novel diet-driven microbial metabolite fecal biomarker following rice bran consumption in mice and humans from this study. Dietary rice bran bioactivity via gut microbiome metabolism in mice and humans contributes to protection against colorectal cancer. The findings from this study provide compelling support for rice bran in clinical and public health guidelines for colorectal cancer prevention and control.

Nickel Complexes Bearing ONS Chelating Ligands: A Promising Contender for In Vitro Cytotoxicity Effects on Human Pancreatic Cancer MIA-PaCa-2 Cells.

The highly chronic human pancreatic cancer cell is one of the major reasons for cancerous death. Nickel complexes are recently gaining interest in anticancer activities on different types of cancer cells. Hence, in this study, we synthesized and characterized a series of ONS donor ligands [2-HO-C6H4-CH═N-(C6H4)-SH] (L1), [2-OH-3-OMe-C6H3-CH═N-(C6H4)-SH] (L2), [2-OH-3,5-(C(Me)3)2-C6H2-CH═N-(C6H4)-SH] (L3), [2-OH-C6H4-CH═N-(C6H4)-SMe] (L4), [2-OH-3-OMe-C6H3-CH═N-(C6H4)-SMe] (L5), [2-OH-3,5-(C(Me)3)2-C6H2-CH═N-(C6H4)-SMe] (L6) and their Ni(II) metal complexes [(MeOH)Ni(L1-L1-4H)] (1), [(MeOH)Ni(L2-L2-4H)] (2), [(MeOH)Ni(L3-L3-4H)] (3), [(L4-H)2Ni] (4), [(L5-H)2Ni] (5), and [(L6-H)2Ni] (6). The single-crystal X-ray diffraction data of complexes 1 and 4 were collected to elucidate the geometry around the metal center. The anticancer activity of complexes 1-6 was investigated on human pancreatic cancer cell line MIA-PaCa-2, which revealed that complexes 4 and 6 were the most significantly effective in decreasing the cell viability of cancer cells at the lowest dose. The structure parameters obtained from single-crystal X-ray diffraction data are found to be in good agreement with the data from density functional theory and Hirshfeld surface analysis for complex 1.

Gender-based effect of absence of gut microbiota on the protective efficacy of Bifidobacterium longum-fermented rice bran diet against inflammation-associated colon tumorigenesis.

Dietary rice bran (RB) has shown capacity to influence metabolism by modulation of gut microbiota in individuals at risk for colorectal cancer (CRC), which warranted attention for delineating mechanisms for bidirectional influences and cross-feeding between the host and RB-modified gut microbiota to reduce CRC. Accordingly, in the present study, fermented rice bran (FRB, fermented with a RB responsive microbe Bifidobacterium longum), and non-fermented RB were fed as 10% w/w (diet) to gut microbiota-intactspf or germ-free micegf to investigate comparative efficacy against inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC. Results indicated both microbiota-dependent and independent mechanisms for RB meditated protective efficacy against CRC that was associated with reduced neoplastic lesion size and local-mucosal/systemic inflammation, and restoration of colonic epithelial integrity. Enrichment of beneficial commensals (such as, Clostridiales, Blautia, Roseburia), phenolic metabolites (benzoate and catechol metabolism), and dietary components (ferulic acid-4 sulfate, trigonelline, and salicylate) were correlated with anti-CRC efficacy. Germ-free studies revealed gender-specific physiological variables could differentially impact CRC growth and progression. In the germ-free females, the RB dietary treatment showed a ∼72% reduction in the incidence of colonic epithelial erosion when compared to the ∼40% reduction in FRB-fed micegf . Ex vivo fermentation of RB did not parallel the localized-protective benefits of gut microbial metabolism by RB in damaged colonic tissues. Findings from this study suggest potential needs for safety considerations of fermented fiber rich foods as dietary strategies against severe inflammation-associated colon tumorigenesis (particularly with severe damage to the colonic epithelium).

The pH-Responsive Liposomes-The Effect of PEGylation on Release Kinetics and Cellular Uptake in Glioblastoma Cells.

Nanomedicine has been, to a certain degree, a success story in the development of superior anticancer therapies. However, there are tumors that remain a huge challenge for nanoformulations, for instance, brain tumors such as glioblastoma, the most common and aggressive brain tumor. To utilize the fact that such tumors are characterized by an acidic extracellular environment, we selected pH-responsive liposomes as a potential drug delivery system for superior delivery to GBM. Liposomes comprising PEGylated lipid of two chain lengths with encapsulated fluorescent marker calcein were characterized and challenged against non-PEGylated vesicles. The in vitro calcein release from three liposomal formulations (<200 nm), namely non-PEGylated (pH-Lip) and PEGylated, pH-Lip−PEG750, and pH-Lip−PEG2000, was followed at three pH conditions to prove the pH-responsiveness. The intracellular delivery of a liposomally encapsulated marker was determined in GL261 glioblastoma cell lines in vitro using both flow cytometry and confocal microscopy. The inclusion of PEG2000 within liposomal formulation resulted in reduced in vitro pH-responsiveness compared to pH-Lip and pH-Lip750. All three pH-responsive liposomal formulations improved intracellular uptake in GL261 cells compared to non-pH-responsive liposomes, with negligible differences regarding PEG length. The proposed formulations should be further evaluated in glioblastoma models.

Characterization of stage-specific tumor progression in TMPRSS2-ERG (fusion)-driven and non-fusion-driven prostate cancer in GEM models.

In the present study, we performed a comparative stage-specific pathological and molecular marker evaluation of TMPRSS2-ERG fusion and PTEN loss-driven (TMPRSS2-ERG. Ptenflox/flox ) versus non-fusion-driven prostate tumorigenesis (Hi-Myc) in mice. Anterior, ventral, and dorsolateral prostates were collected from mice at different ages (or time points post-Cre induction). Results indicated that growth and progression of prostatic intraepithelial lesions to adenocarcinoma stages occurred in both mice models albeit at different rates. In the TMPRSS2-ERG. Ptenflox/flox mice, the initiation of tumorigenesis was slow, but subsequent progression through different stages became increasingly faster. Adenocarcinoma stage was reached early on; however, no high-grade undifferentiated tumors were observed. Conversely, in the Hi-Myc+/- mice, tumorigenesis initiation was rapid; however, progression through different stages was relatively slower and it took a while to reach the more aggressive phenotype stage. Nevertheless, at the advanced stages in the Hi-Myc+/- mice, high-grade undifferentiated tumors were observed compared to the later stage tumors observed in the fusion-driven TMPRSS2-ERG. Ptenflox/flox mice. These results were corroborated by the stage specific-pattern in the molecular expression of proliferation markers (PCNA and c-Myc); androgen receptor (AR); fusion-resultant overexpression of ERG; Prostein (SLC45-A3); and angiogenesis marker (CD-31). Importantly, there was a significant increase in immune cell infiltrations, which increased with the stage of tumorigenesis, in the TMPRSS2-ERG fusion-positive tumors relative to fusion negative tumors. Together, these findings are both novel and highly significant in establishing a working preclinical model for evaluating the efficacy of interventions during different stages of tumorigenesis in TMPRSS2-ERG fusion-driven PCa.

Stage-specific differential expression of zinc transporter SLC30A and SLC39A family proteins during prostate tumorigenesis.

Prostate cancer (PCa) initiation and progression uniquely modify the prostate milieu to aid unrestrained cell proliferation. One salient modification is the loss of the ability of prostate epithelial cells to accumulate high concentrations of zinc; however, molecular alterations associated with loss of zinc accumulating capability in malignant prostate cells remain poorly understood. Herein, we assessed the stage-specific expression of zinc transporters (ZNTs) belonging to the ZNT (SLC30A) and Zrt- and Irt-like protein (ZIP) (SLC39A) solute-carrier family in the prostate tissues of different genetically engineered mouse models (GEMM) of PCa (TMPRSS2-ERG.Ptenflox/flox , Hi-Myc+/- , and transgenic adenocarcinoma of mouse prostate), their age-matched wild-type controls, and 104 prostate core biopsies from human patients with different pathological lesions. Employing immunohistochemistry, differences in the levels of protein expression and spatial distribution of ZNT were evaluated as a function of the tumor stage. Results indicated that the expression of zinc importers (ZIP1, ZIP2, and ZIP3), which function to sequester zinc from circulation and prostatic fluid, was low to negligible in the membranes of the malignant prostate cells in both GEMM and human prostate tissues. Regarding zinc exporters (ZNT1, ZNT2, ZNT9, and ZNT10) that export excess zinc into the extracellular spaces or intracellular organelles, their expression was low in normal prostate glands of mice and humans; however, it was significantly upregulated in prostate adenocarcinoma lesions in GEMM and PCa patients. Together, our findings provide new insights into altered expression of ZNTs during the progression of PCa and indicate that changes in zinc homeostasis could possibly be an early-initiation event during prostate tumorigenesis and a likely prevention/intervention target.

An Annexin V-FITC-Propidium Iodide-Based Method for Detecting Apoptosis in a Non-Small Cell Lung Cancer Cell Line.

Annexin V and propidium iodide staining is widely used for determining the cellular death through apoptosis. In the presence of Ca2+ ions, annexin V has a strong binding affinity for phosphatidylserine, a membrane phospholipid that during apoptosis is translocated from the inner side of the cell membrane to its outer side. On the other hand, propidium iodide has ability for DNA binding and it can only enter into necrotic or late apoptotic cells. This chapter describes a commonly used method for detection of apoptosis in a non-small cell lung cancer cell line using annexin V and propidium iodide dye. We describe the detection of different stages of apoptosis in the A549 lung cancer cell line treated with dihydroartemisinin (DHA). This apoptosis detection method can be used to determine the efficacy of different kinds of drugs on cultured cancer cell lines.

Modulation of immune response and enhanced clearance of Salmonella typhi by delivery of Vi polysaccharide conjugate using PLA nanoparticles.

Polysaccharide antigens do not promote antibody class switching and memory antibody response, thus require conjugation with a T cell dependent carrier protein to generate protective immune response. The intensity of immune responses varies with the carrier proteins for the same carbohydrate antigen and most of the carrier proteins do not generate strong immune responses. Vi polysaccharide and r-flagellin of Salmonella typhi were conjugated and formulated in PLA particles as nanoglycoconjugate which not only generated strong immune response but also promoted antibody class switching and elicited memory antibody response from single point immunization. Nanoglycoconjugate immunization also modulate anti-inflammatory property of Vi polysaccharide with an enhance secretion of pro-inflammatory cytokine TNF-α and IL-6. This was with concomitant decrease of IFN-γ production, antibody class switching from IgG3 to IgG2 with memory antibody generation against Vi polysaccharide. Antibody elicited by nanoglycoconjugate showed better opsonization and clearance of Salmonella typhi in THP-1 macrophages as compared to Vi-flagellin glycoconjugate and Vi TT (Typhbar®). Delivery of glycoconjugate through nanoparticles provides a platform technology for improving the immunogenicity of polysaccharide based vaccines.

Ajmalicine and Reserpine: Indole Alkaloids as Multi-Target Directed Ligands Towards Factors Implicated in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disorder characterized by exponential loss of memory and cognitive deficit involving several disease modifying targets (amyloid beta, beta-secretase, monoaminoxidase-B, and cholinesterase). The present study explores multi-target directed ligand approach using secondary metabolite reserpine (RES) and ajmalicine (AJM) obtained from Rauwolfia serpentina roots. Novel LCMS and HPLC methods were developed for identification and quantification of reserpine and ajmalicine. In vitro enzyme inhibition assays were performed to evaluate anti-cholinesterase, ß-site amyloid cleaving enzyme (BACE-1) inhibition and monoamine oxidase-B (MAO-B) inhibition, further analyzed with in silico analysis. Anti-amyloidogenic potential was studied using anti-aggregation studies along with TEM and circular dichroism (CD) analysis. In vitro neuroprotective potential against Aß toxicity and anti-oxidative stress was demonstrated using PC12 cell cultures. Reserpine is a more potent dual cholinesterase inhibitor than ajmalicine (IC50 values of 1.7 µM (AChE) and 2.8 µM (BuChE)). The anti-aggregation activity of reserpine (68%) was more than ajmalicine (56%). Both compounds demonstrated neuroprotective activity against Aß42 (92%) and H2O2 (93%) induced toxicity in PC12 cells against controls. Phytocompounds also inhibited MAO-B and BACE-1 enzymes in concentration dependent manner. Molecular docking studies indicated the strong binding of compounds to the catalytic site of targets. This novel study demonstrated that reserpine and ajmalicine as a multi-target directed ligand that have disease modifying potential for amelioration of AD.

Immunogenicity and contraceptive efficacy of recombinant fusion protein encompassing Sp17 spermatozoa-specific protein and GnRH: Relevance of adjuvants and microparticles based delivery to minimize number of injections.

PROBLEM: Requirement of multiple injections of contraceptive vaccines to achieve infertility is one of the important impediments for their application. In the present study, attempts have been made to reduce the number of injections of contraceptive vaccine. METHOD OF STUDY: Fusion protein encompassing C-terminus fragment of sperm protein Sp17 (aa residues 76-126) and two copies of gonadotropin-releasing hormone along with T-cell epitopes and dilysine linkers (abbreviated as Sp17C -GnRH2 ) was expressed in Escherichia coli. Its immunogenicity and contraceptive efficacy have been evaluated in female FVB/J mice using different adjuvants and delivery platforms. RESULTS: Immunization of female mice with recombinant Sp17C -GnRH2 (25 µg/injection/mouse) emulsified with squalene-arlacel A following two injections schedule led to failure of 88.8% immunized animals to conceive, which was not significantly different from mice immunized with same protein along with alum following three injections schedule. To make single-dose vaccine, poly d,l-lactic acid-based microparticles (PLA-MPs) entrapping Sp17C -GnRH2 were prepared. Immunization of female mice with a combination of soluble Sp17C -GnRH2 (12.5 µg/injection/mouse) along with Sp17C -GnRH2 entrapped in PLA-MPs (12.5 µg/injection/mouse) in alum showed higher antibody titres and contraceptive efficacy as compared to mice immunized with Sp17C -GnRH2 entrapped in PLA-MPs alone in alum. Immunization with recombinant Sp17C -GnRH2 led to long-term infertility as second mating (150 days after immunization) of various groups of immunized mice showed similar infertility as observed during first mating. CONCLUSION: Single-dose immunization with PLA-MPs entrapping Sp17C -GnRH2 along with soluble recombinant protein in alum generated long-lasting infertility in female mice.

Hyaluronic acid - dihydroartemisinin conjugate: Synthesis, characterization and in vitro evaluation in lung cancer cells.

In recent years, a great deal of attention has been given towards re-purposing and re-innovating the potential drugs. In this regard, dihydroartemisinin (DHA) has been reported to demonstrate anti-proliferative effects on various cancerous cells viz. breast, liver and lung. However, it is associated with some limitations, such as low bioavailability which is hampered by its poor aqueous solubility and its rapid metabolism in systemic circulation. Therefore, in order to overcome these limitations, we synthesized a novel hyaluronic acid-dihydroartemisinin conjugate in which the hydroxyl group of DHA was covalently linked to carboxylic group of hyaluronic acid (HA). The conjugate was successfully characterized using 1H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel permeation chromatography (GPC). The synthesized conjugate self-assembled into nanoparticles in aqueous solution. The developed nanoparticles were characterized for their average size, zeta potential, Transmission Electron Microscopy (TEM), X-ray Powder Diffraction (XRD) and loading efficiency. The nanoparticles were cytotoxic to lung cancer (A549) cell line which was determined using CCK-8 cell viability assay. This was further supported by Annexin-V-FITC-Propidium iodide apoptosis assay, reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss. Conclusively, present findings demonstrate hyaluronic acid conjugates can be used to improve the therapeutic outcomes of anticancer drugs.

Gemcitabine and betulinic acid co-encapsulated PLGA-PEG polymer nanoparticles for improved efficacy of cancer chemotherapy.

The present study demonstrated the development of gemcitabine and betulinic acid co-encapsulated PLGA-PEG polymer nanoparticles for enhancing the chemotherapeutic response. This combinatorial PLGA-PEG nanoparticle was formulated using double emulsion and had size <200 nm. The developed nanoparticles were characterized using dynamic light scattering and transmission electron microscopy for their size and shape, respectively. The in vitro release of the drugs from combinatorial nanoparticles was predominantly followed by Fickian diffusion phenomenon. Study on hemocompatibilty approved the administration of this combinatorial nanoparticle for animal study. In vitro cytotoxicity study on Panc1 cells using MTT assay, reactive oxygen species production and cellular apoptotic assay demonstrated that combinatorial nanoparticle was more cytotoxic compared to native drugs solution. Furthermore, the combinatorial nanoparticle suppressed tumor growth more efficiently in Ehrlich (solid) tumor model than the native gemcitabine and betulinic acid at the same concentrations. These findings indicated that PLGA-PEG nanoparticle might be used to co-deliver multiple chemotherapeutic drugs with different properties for enhancing antitumor efficacy.

Highly Biocompatible, Fluorescence, and Zwitterionic Carbon Dots as a Novel Approach for Bioimaging Applications in Cancerous Cells.

Highly biocompatible, excellently photostable, nitrogen- and sulfur-containing novel zwitterionic carbon dots (CDs) were synthesized by microwave-assisted pyrolysis. The size of CDs were 2-5 nm, with an average size of 2.61 ± 0.7 nm. CDs were characterized by UV/vis spectroscopy, fluorescence spectroscopy, zeta potential, Fourier-transform infrared spectroscopy, X-ray diffraction, and time-resolved fluorescence spectroscopy. CDs were known to emit blue fluorescence when excited at 360 nm, that is, UV region, and emit in the blue region of visible spectrum, that is, at 443 nm. CDs showed excitation-independent photoluminescence behavior and were highly fluorescent even at lower concentration under UV light. These CDs were highly fluorescent in nature, with the quantum yield being as high as 80%, which is comparable to that of organic dyes. The CDs were further used to image two different oral cancer cell lines, namely, FaDu (human pharyngeal carcinoma) and Cal-27 (human tongue carcinoma). The cell viability assay demonstarted that CDs were highly biocompatible, which was further confirmed by the side scattering studies as no change in the granularity was observed even at the highest concentration of 1600 µg/mL. The generation of reactive oxygen species (ROS) was also investigated and negligible generaton of ROS was detected. In addition to that, the uptake phenomenon, cell cycle analysis, exocytosis, and cellular uptake at 4 °C and in the presence of ATP inhibitor were studied. It was found that CDs easily cross the plasma membrane without hampering the cellular integrity.

CD44 targeted PLGA nanomedicines for cancer chemotherapy.

In recent years scientific community has drawn a great deal of attention towards understanding the enigma of cluster of differentiation-44 (CD44) in order to deliver therapeutic agents more selectively towards tumor tissues. Moreover, its over-expression in variety of solid tumors has attracted drug delivery researchers to target this receptor with nanomedicines. Conventional nanomedicines based on biodegradable polymers such as poly(lactide-co-glycolide) (PLGA) are often associated with insufficient cellular uptake by cancer cells, due to lack of active targeting moiety on their surface. Therefore, to address this limitation, CD44 targeted PLGA nanomedicines has gained considerable interest for enhancing the efficacy of chemotherapeutic agents. In this review, we have elaborately discussed the recent progress in the design and synthesis of CD44 targeted PLGA nanomedicines used to improve tumor-targeted drug delivery. We have also discussed strategies based on co-targeting of CD44 with other targeting moieties such as folic acid, human epidermal growth factor 2 (HER2), monoclonal antibodies using PLGA based nanomedicines.

Recent advances in near-infrared light-responsive nanocarriers for cancer therapy.

In recent years, research has focused on the development of smart nanocarriers that can respond to specific stimuli. Among the various stimuli-responsive platforms for cancer therapy, near-infrared (NIR) light (700-1000nm)-responsive nanocarriers have gained considerable interest because of their deeper tissue penetration capacity, precisely controlled drug release, and minimal damage towards normal tissues. In this review, we outline various therapeutic applications of NIR-responsive nanocarriers in drug delivery, photothermal therapy (PTT), photodynamic therapy (PDT), and bioimaging. We also highlight recent trends towards NIR-responsive combinatorial therapy and multistimuli-responsive nanocarriers for improving therapeutic outcomes.

Therapeutic applications of betulinic acid nanoformulations.

Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad-spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half-life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half-life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems-including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes-have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.

Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy.

The clinical application of betulinic acid (BA), a natural pentacyclic triterpenoid with promising antitumor activity, is hampered due to its extremely poor water solubility and relatively short half-life in the systemic circulation. In order to address these issues, herein, we developed betulinic acid loaded polylactide-co-glycolide- monomethoxy polyethylene glycol nanoparticles (PLGA-mPEG NPs). The PLGA-mPEG co-polymer was synthesized and characterized using NMR and FT-IR. BA loaded PLGA-mPEG NPs were prepared by an emulsion solvent evaporation method. The developed nanoparticles had a desirable particle size (∼147nm) and exhibited uniform spherical shape under transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The PLGA-mPEG NPs were able to decrease the uptake by macrophages (i.e. J774A.1 and Raw 264.7 cells) as compared to PLGA nanoparticles. In vitro cytotoxicity in MCF7 and PANC-1 cells demonstrated enhanced cytotoxicity of BA loaded PLGA-mPEG NPs as compared to free BA. The cellular uptake study in both the cell lines demonstrated time dependent uptake behavior. The enhanced cytotoxicity of BA NPs was also supported by increased cellular apoptosis, mitochondrial membrane potential loss, generation of high reactive oxygen species (ROS) and cell cycle arrest. Further, intravenous pharmacokinetics study revealed that BA loaded PLGA-mPEG NPs could prolong the circulation of BA and remarkably enhance half-life by ∼7.21 folds. Consequently, in vivo studies in Ehrlich tumor (solid) model following intravenous administration demonstrated superior antitumor efficacy of BA NPs as compared to native BA. Moreover, BA NPs treated Ehrlich tumor mice demonstrated no biochemical, hematological and histological toxicities. These findings collectively indicated that the BA loaded PLGA-mPEG NPs might serve as a promising nanocarrier for improved therapeutic efficacy of betulinic acid.