Smart Cancer Nanomedicine for Synergetic Therapy.

Cancer is the second leading cause of death. Notwithstanding endeavors to comprehend tumor causes and therapeutic modalities, no noteworthy advancements in cancer therapy have been identified. Nanomedicine has drawn interest for its diagnostic potential because of its ability to deliver therapeutic agents specifically to tumors with little adverse effects. Nanomedicines have become prevalent in the treatment of cancer. Here, we present four strategic suggestions for improvement in the functionality and use of nanomedicine. (1) Smart drug selection is a prerequisite for both medicinal and commercial achievement. Allocating resources to the advancement of modular (pro)drugs and nanocarrier design ought to consider the role of opportunistic decisions depending on drug availability. (2) Stimuli-responsive nanomedicine for cancer therapy is being designed to release medications at particular locations precisely. (3) The cornerstone of clinical cancer treatment is combination therapy. Nanomedicines should be included more frequently in multimodal combination therapy regimens since they complement pharmacological and physical co-treatments. (4) Regulation by the immune system is transforming cancer therapy. Nanomedicines can improve the effectiveness of the immune system and control the behavior of anticancer immunity. These four approaches, both separately and particularly in combination, will accelerate and promote the creation of effective cancer nanomedicine treatments.

A clinical perspective of chitosan nanoparticles for infectious disease management.

Infectious diseases and their effective management are still a challenge in this modern era of medicine. Diseases, such as the SARS-CoV-2, Ebola virus, and Zika virus, still put human civilization at peril. Existing drug banks, which include antivirals, antibacterial, and small-molecule drugs, are the most advocated method for treatment, although effective but they still flounder in many instances. This calls for finding more effective alternatives for tackling the menace of infectious diseases. Nanoformulations are progressively being implemented for clinical translation and are being considered a new paradigm against infectious diseases. Natural polymers like chitosan are preferred to design nanoparticles owing to their biocompatibility, biodegradation, and long shelf-life. The chitosan nanoparticles (CNPs) being highly adaptive delivers contemporary prevention for infectious diseases. Currently, they are being used as antibacterial, drug, and vaccine delivery vehicles, and wound-dressing materials, for infectious disease treatment. Although the recruitment of CNPs in clinical trials associated with infectious diseases is minimal, this may increase shortly due to the sudden emergence of unknown pathogens like SARS-CoV-2, thus turning them into a panacea for the management of microorganisms. This review particularly focuses on the all-around application of CNPs along with their recent clinical applications in infectious disease management.

Nanoparticle-based CRISPR/Cas Delivery: An Emerging Tactic for Cancer Therapy.

Genome editing arose as a new promising approach for treating numerous intricate ailm ents including cancer. Over the past couple of decades, delivery technologies that have serendipitously been developed using viral vectors are successful to some extent in protein and nucleic acid delivery but their effectiveness still lags due to their efficiency, tissue targeting capabilities, and toxicity which must be further improved. With the infiltration of nanotechnology into every sphere of life, nano-vehicles can be implemented as an ideal modality that can overcome challenges, also can be introspective as new genome editing tools for cancer therapy owing to the safety and efficiency in clinical settings. Such projected substitution can help in developing highly efficacious therapy regimes which are successful in clinical settings. This emerging approach of incorporation of genome editors (CRISPR/Cas) in different nano vehicles and their utility in targeting various aspects of cancer therapy like treatment, diagnostics, modelling has been comprehensively done in this review.

Hypoxia responsive phytonanotheranostics: A novel paradigm towards fighting cancer.

Hypoxia enhances tumor aggressiveness, thereby reducing the efficacy of anticancer therapies. Phytomedicine, which is nowadays considered as the new panacea owing to its dynamic physiological properties, is often plagued by shortcomings. Incorporating these wonder drugs in nanoparticles (phytonanomedicine) for hypoxia therapy is a new prospect in the direction of cancer management. Similarly, the concept of phytonanotheranostics for the precise tumor lesion detection and treatment monitoring in the hypoxic scenario is going on a rampant speed. In the same line, smart nanoparticles which step in for "on-demand" drug release based on internal or external stimuli are also being explored as a new tool for cancer management. However, studies regarding these smart and tailor-made nanotheranostics in the hypoxic tumor microenvironment are very limited. The present review is an attempt to collate these smart stimuli-responsive phytonanotherapeutics in one place for initiating future research in this upcoming field for better cancer treatment.

Nanobiosensor-based diagnostic tools in viral infections: Special emphasis on Covid-19.

The rapid propagation of novel human coronavirus 2019 and its emergence as a pandemic raising morbidity calls for taking more appropriate measures for rapid improvement of present diagnostic techniques which are time-consuming, labour-intensive and non-portable. In this scenario, biosensors can be considered as a means to outmatch customary techniques and deliver point-of-care diagnostics for many diseases in a much better way owing to their speed, cost-effectiveness, accuracy, sensitivity and selectivity. Besides this, these biosensors have been aptly used to detect a wide spectrum of viruses thus facilitating timely delivery of correct therapy. The present review is an attempt to analyse such different kinds of biosensors that have been implemented for virus detection. Recently, the field of nanotechnology has given a great push to diagnostic techniques by the development of smart and miniaturised nanobiosensors which have enhanced the diagnostic procedure and taken it to a new level. The portability, hardiness and affordability of nanobiosensor make them an apt diagnostic agent for different kinds of viruses including SARS-CoV-2. The role of such novel nanobiosensors in the diagnosis of SARS-CoV-2 has also been addressed comprehensively in the present review. Along with this, the challenges and future position of developing such ultrasensitive nanobiosensors which should be taken into consideration before declaring these nano-weapons as the ideal futuristic gold standard of diagnosis has also been accounted for here.

Smart nanotheranostic hydrogels for on-demand cancer management.

Theranostics is a revolution in cancer therapy. Hydrogels have many implications as a drug delivery vehicle and theranostics hydrogels could be a model nanotherapeutic for simultaneous cancer diagnosis and treatment.

Recent trends of nanomedicinal approaches in clinics.

Nanotechnology has become the indispensable cutting edge science providing solutions to many problems associated with human being. The application of nanotechnology associated to human health "nanomedicine" has revolutionized the drug delivery system by providing improved pharmacological and therapeutic properties of drugs. These advantageous effects of drug loaded nanocarrier systems are embraced by the pharmaceutical industries for the development of different effective nanocarriers. Currently, several drug loaded nanoformulations are approved by the Food and Drug Administration (FDA), and some of them are undergoing clinical trials for the human use. In this review, we have discussed the progress achieved so far for various drug loaded nanoformulations along with few emerging nanoformulations that are about to enter into clinical trials.

Exploitation of redox discrepancy in leukemia cells by a reactive oxygen species nanoscavenger for inducing cytotoxicity in imatinib resistant cells.

Chronic myeloid leukemia (CML) has been the hub of exhilarating progress in cancer therapy with the advent of imatinib mesylate. However, therapeutic selectivity and drug resistance are two major issues in imatinib based leukemia therapy prompting development of strategies to surmount imatinib resistance for effective CML therapy. Growing evidences advocate that, cancer cells exhibit augmented intrinsic reactive oxygen species (ROS), due to oncogenic stimulation, amplified metabolic activity, and mitochondrial dysfunction. Since ROS activates multidrug resistant proteins in CML cells, we hypothesized that an herbal molecule having ROS scavenging property may therefore enhance imatinib induced cell death in drug resistant cells by counteracting ROS mediated drug resistance. In the present study, we document to explore an approach to simultaneously deliver two drugs (imatinib, an anticancer drug for CML therapy and curcumin a ROS scavenger) using poly (lactide-co-glycolide) (PLGA) nanoparticles for drug resistant CML cells. Such a combinational approach will help to enhance the therapeutic efficacy of imatinib by utilizing ROS scavenging properties of curcumin in imatinib resistant cell line thereby sensitizing them to chemotherapy by activating alternative modalities of cell death.

Sustained targeting of Bcr-Abl + leukemia cells by synergistic action of dual drug loaded nanoparticles and its implication for leukemia therapy.

Chimeric Bcr-Abl oncoprotein is the molecular hallmark of chronic myeloid leukemia (CML) and hence a lucrative target for therapeutic intervention of CML.However, limited efficacy of current first line treatment for CML calls attention for further development of more efficient strategies. Recently, much attention has been given to nanoparticle (NP) based drug delivery systems loaded with dual drugs to improve current disease therapies by overcoming toxicity and other side effects associated with high doses of single drugs. In the present study, we document to explore an approach to simultaneously deliver two drugs at target sites (i.e. Bcr-Abl oncoprotein) using poly (lactide-co-glycolide) (PLGA) nanoparticles. Preliminary study included screening six different anticancer drugs and their nanoformulations on leukemia cells. Results confirmed superlative antileukemic activity of paclitaxel (especially in formulations) on model cell line K562, but only upon longer exposure. Thus to lower time of action of such a potent drug, different drug combination were experimented taking the advantage of synergistic action of both the drugs. Evaluation at molecular and genetic level helped to identify signaling pathways upstream and downstream of Bcr-Abl, leading to its suppression. Results helped to illustrate dynamic changes primarily involved in inducing apoptotic activities on drug exposure of leukemia cells, thereby facilitating us to integrate different drug combinations in a more specific manner in near future to study CML in clinical settings.

Enhanced antiproliferative activity of Herceptin (HER2)-conjugated gemcitabine-loaded chitosan nanoparticle in pancreatic cancer therapy.

Currently, effective drug delivery in pancreatic cancer treatment is a major challenge. Nanomedicine plays an essential role by delivering anticancer drugs in a targeted manner to the malignant tumor cells, leading to increased efficacy by reducing the toxicity of anticancer drugs to normal, sensitive sites. This study investigated the preparation and characterization of a targeted system represented by Herceptin-conjugated gemcitabine-loaded chitosan nanoparticles (HER2-Gem-CS-NPs) for pancreatic cancer therapy. The targeted NPs displayed superior antiproliferative activity along with an enhanced S-phase arrest, leading to apoptosis in comparison with unconjugated gemcitabine-loaded nanoparticles and free gemcitabine due to higher cellular binding with eventual uptake and prolonged intracellular retention. Thus, HER2-Gem-CS-NPs are able to provide an efficient and targeted delivery of gemcitabine for pancreatic cancer treatment. FROM THE CLINICAL EDITOR: This study investigated the preparation and characterization of a targeted drug delivery system consisting of Herceptin-conjugated gemcitabine-loaded chitosan nanoparticles for pancreatic cancer therapy.

PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect.

As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity.

Cancer nanotechnology: application of nanotechnology in cancer therapy.

The application of nanotechnology for cancer therapy has received considerable attention in recent years. Cancer nanotechnology (an interdisciplinary area of research in science, engineering and medicine) is an upcoming field with extensive applications. It provides a unique approach and comprehensive technology against cancer through early diagnosis, prediction, prevention, personalized therapy and medicine. Target-specific drug therapy and methods for early diagnosis of pathologies are the priority research areas in which nanotechnology would play a vital part. This review focuses on the approaches of cancer nanotechnology in the advancement of cancer therapy.

Curcumin-encapsulated MePEG/PCL diblock copolymeric micelles: a novel controlled delivery vehicle for cancer therapy.

AIM: To develop a suitable formulation of curcumin-encapsulated methoxy poly(ethylene glycol) (MePEG)/poly-epsilon-caprolactone (PCL) diblock copolymeric micelle by varying the copolymer ratio, for achieving small sized micelles with high encapsulation of curcumin. To evaluate the micelle's aqueous solubility and stability, efficiency of cellular uptake, cell cytotoxicity and ability to induce apoptosis on pancreatic cell lines. METHOD: Amphiphilic diblock copolymers (composed of MePEG and PCL) were used in various ratios for the preparation of curcumin-encapsulated micelles using a modified dialysis method. Physicochemical characterization of the formulation included size and surface charge measurement, transmission electron microscopy characterization, spectroscopic analysis, stability and in vitro release kinetics studies. The anticancer efficacy of the curcumin-encapsulated micelle formulation was compared with unmodified curcumin in terms of cellular uptake, cell cytotoxicity and apoptosis of pancreatic cell lines MIA PaCa-2 and PANC-1. RESULTS: Physiochemical characterization of the formulations revealed that curcumin was efficiently encapsulated in all formulation of MePEG/PCL micelles; however, a 40:60 MePEG:PCL ratio micelle was chosen for experimental studies owing to its high encapsulation (approximately 60%) with size (approximately 110 nm) and negative zeta potential (approximately -16 mV). Curcumin-encapsulated micelles increased the bioavailability of curcumin due to enhanced uptake (2.95 times more compared with unmodified) with comparative cytotoxic activity (by induction of apoptosis) compared with unmodified curcumin at equimolar concentrations. IC(50) values for unmodified curcumin and curcumin micelles were found to be 24.75 microM and 22.8 microM for PANC-1 and 14.96 microM and 13.85 microM for MIA PaCa-2, respectively. Together the results clearly indicate the promise of a micellar system for efficient solubilization, stabilization and controlled delivery of the hydrophobic drug curcumin for cancer therapy.

Targeted epidermal growth factor receptor nanoparticle bioconjugates for breast cancer therapy.

Selective drug delivery is an important approach with great potential for overcoming problems associated with the systemic toxicity and poor bioavailability of antineoplastic drugs. Nanomedicine plays a pivotal role by delivering drugs in a targeted manner to the malignant tumor cells thereby reducing the systemic toxicity of the anticancer drugs. The objective of this study was to prepare and characterize rapamycin loaded polymeric poly(lactide-co-glycolide) (PLGA) nanoparticles (NP) that were surface conjugated with antibodies to epidermal growth factor receptor (EGFR), highly expressed on breast cancer cells, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) mediated cross linking agents. To potentiate the anticancer efficiency of the formulations, in vitro cytotoxicity of native rapamycin, rapamycin loaded nanoparticles and EGFR antibody conjugated rapamycin loaded nanoparticles (EGFR-Rapa-NPs) were evaluated on malignant MCF 7 breast cancer cell lines. IC(50) doses as determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay showed the superior antiproliferative activity of EGFR-Rapa-NPs over unconjugated nanoparticles and native rapamycin due to higher cellular uptake on malignant breast cancer cells. Cell cycle arrest and cellular apoptosis induced by the above formulations were confirmed by flow cytometry. Molecular basis of apoptosis studied by western blotting revealed the involvement of a cytoplasmic protein in activating the programmed cell death pathway. Thus it was concluded that EGFR-Rapa-NPs provide an efficient and targeted delivery of anticancer drugs, presenting a promising active targeting carrier for tumor selective therapeutic treatment in near future.

Sustained antibacterial activity of doxycycline-loaded poly(D,L-lactide-co-glycolide) and poly(epsilon-caprolactone) nanoparticles.

AIM: To increase the entrapment efficiency of doxycycline (DXY)-loaded poly(D,L-lactide-co-glycolide) (PLGA):poly(epsilon-caprolactone) (PCL) nanoparticles by up to 70% by varying the different formulation parameters such as polymer ratio, amount of drug loading (w/w), solvent selection, electrolyte addition and pH in the formulation. METHOD: Biodegradable polymers PLGA and PCL are used in various ratios for nanoparticle preparation using the water-in-oil-in-water double emulsion technique for water-soluble DXY. The physicochemical characterization of nanoparticles included size and surface charge measurement, study of surface morphology using scanning-electron microscopy, Fourier transform infrared spectroscopy study, differential scanning calorimetry analysis and in vitro release kinetics study. RESULTS: The mean particle size ranged from 230 to 360 nm, as measured by dynamic laser light scattering, and scanning-electron microscopy confirmed the spherical nature and smooth surface of the nanoparticles. Fourier transform infrared spectroscopy analysis of void nanoparticles, drug-loaded nanoparticles and native DXY indicated no interaction between the drug and polymer in the nanoparticle. Differential scanning calorimetry analysis of drug-loaded nanoparticles indicated a molecular level dispersion of DXY in the formulation. The antibacterial activity of native DXY and DXY-loaded nanoparticles were tested using a strain of Escherichia coli (DH5alpha) through growth inhibition and colony-counting method. The results indicated that DXY-loaded nanoparticles are more effective than native DXY due to the sustained release of DXY from nanoparticles in the E. coli strain.