Role of Vitamins in Therapeutic and Targeting Approaches for Prostate Cancer: An Overview.

Vitamins play a crucial role in cellular functions like cell cycling and proliferation, differentiation, and apoptosis. These also help in the induction of cell cycle arrest and/or apoptosis. They can inhibit normal prostatic epithelial cell growth and might be helpful for the prevention of prostate cancer (PCa). Many essential vitamins including the fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K) and the water-soluble vitamins (vitamin B complexes and vitamin C) have a huge impact on the inhibition of growth and progression of PCa. Vitamins show anticancer properties and are involved in regulatory processes like the DNA repairing process, which inhibit the growth of PCa. Consumption of multivitamins prevents methylation of cancer cells and possesses an enormous potential that can be applied for the prevention as well as in the management of PCa. They have a great role in the inhibition of different signalling pathways involved in PCa. Moreover, they have also displayed a significant role in targeting of PCa with various nanocarrier systems. This review encompasses the recent studies about the individual actions of different vitamins and vitamin analogs, the combination of vitamins, and their efficient functions in various therapeutic and targeting approaches for PCa.

Recent Update on Nanocarrier(s) as the Targeted Therapy for Breast Cancer.

Despite ongoing advances in cancer therapy, the results for the treatment of breast cancer are not satisfactory. The advent of nanotechnology promises to be an essential tool to improve drug delivery effectiveness in cancer therapy. Nanotechnology provides an opportunity to enhance the treatment modality by preventing degradation, improving tumour targeting, and controlling drug release. Recent advances have revealed several strategies to prevent cancer metastasis using nano-drug delivery systems (NDDS). These strategies include the design of appropriate nanocarriers loaded with anti-cancer drugs that target the optimization of physicochemical properties, modulate the tumour microenvironment, and target biomimetic techniques. Nanocarriers have emerged as a preferential approach in the chemotropic treatment for breast cancer due to their pivotal role in safeguarding the therapeutic agents against degradation. They facilitate efficient drug concentration in targeted cells, surmount the resistance of drugs, and possess a small size. Nevertheless, these nanocarrier(s) have some limitations, such as less permeability across the barrier and low bioavailability of loaded drugs. To overcome these challenges, integrating external stimuli has been employed, encompassing infrared light, thermal stimulation, microwaves, and X-rays. Among these stimuli, ultrasound-triggered nanocarriers have gained significant attention due to their cost-effectiveness, non-invasive nature, specificity, ability to penetrate tissues, and capacity to deliver elevated drug concentrations to intended targets. This article comprehensively reviews recent advancements in different nanocarriers for breast cancer chemotherapy. It also delves into the associated hurdles and offers valuable insights into the prospective directions for this innovative field.

Enhancement of Oral Bioavailability of Protein and Peptide by Polysaccharide-based Nanoparticles.

Oral drug delivery is a prevalent and cost-effective method due to its advantages, such as increased drug absorption surface area and improved patient compliance. However, delivering proteins and peptides orally remains a challenge due to their vulnerability to degradation by digestive enzymes, stomach acids, and limited intestinal membrane permeability, resulting in poor bioavailability. The use of nanotechnology has emerged as a promising solution to enhance the bioavailability of these vital therapeutic agents. Polymeric NPs, made from natural or synthetic polymers, are commonly used. Natural polysaccharides, such as alginate, chitosan, dextran, starch, pectin, etc., have gained preference due to their biodegradability, biocompatibility, and versatility in encapsulating various drug types. Their hydrophobic-hydrophilic properties can be tailored to suit different drug molecules.

Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.

Prostate cancer remains a significant global health concern, requiring innovative approaches for improved therapeutic outcomes. In recent years, nanoparticle-based drug delivery systems have emerged as promising strategies to address the limitations of conventional cancer chemotherapy. The key trends include utilizing nanoparticles for enhancing drug delivery to prostate cancer cells. Nanoparticles have some advantages such as improved drug solubility, prolonged circulation time, and targeted delivery of drugs. Encapsulation of chemotherapeutic agents within nanoparticles allows for controlled release kinetics, reducing systemic toxicity while maintaining therapeutic efficacy. Additionally, site-specific accumulation within the prostate tumor microenvironment is made possible by the functionalization of nanocarrier with targeted ligands, improving therapeutic effectiveness. This article highlights the basics of prostate cancer, statistics of prostate cancer, mechanism of multidrug resistance, targeting approach, and different types of nanocarrier used for the treatment of prostate cancer. It also includes the applications of nanocarriers for the treatment of prostate cancer and clinical trial studies to validate the safety and efficacy of the innovative drug delivery systems. The article focused on developing nanocarrier-based drug delivery systems, with the goal of translating these advancements into clinical applications in the future.

Exploring modified chitosan-based gene delivery technologies for therapeutic advancements.

One of the critical steps in gene therapy is the successful delivery of the genes. Immunogenicity and toxicity are major issues for viral gene delivery systems. Thus, non-viral vectors are explored. A cationic polysaccharide like chitosan could be used as a nonviral gene delivery vector owing to its significant interaction with negatively charged nucleic acid and biomembrane, providing effective cellular uptake. However, the native chitosan has issues of targetability, unpacking ability, and solubility along with poor buffer capability, hence requiring modifications for effective use in gene delivery. Modified chitosan has shown that the "proton sponge effect" involved in buffering the endosomal pH results in osmotic swelling owing to the accumulation of a greater amount of proton and chloride along with water. The major challenges include limited exploration of chitosan as a gene carrier, the availability of high-purity chitosan for toxicity reduction, and its immunogenicity. The genetic drugs are in their infancy phase and require further exploration for effective delivery of nucleic acid molecules as FDA-approved marketed formulations soon.

Antibody-conjugated pH-sensitive liposomes for HER-2 positive breast cancer: development, characterization, in vitro and in vivo assessment.

The object of the current study was to develop and evaluate trastuzumab-conjugated Paclitaxel (PTX) and Elacridar (ELA)-loaded PEGylated pH-sensitive liposomes (TPPLs) for site-specific delivery of an anticancer drug. In this study, paclitaxel is used as an anticancer drug which promotes microtubules polymerization and arrest cell cycle progression at mitosis and subsequently leading to cell death. The single use of PTX causes multiple drug resistance (MDR) and results failure of the therapy. Hence, the combination of PTX and P-glycoprotein inhibitor (ELA) are used to achieve maximum therapeutic effects of PTX. Moreover, monoclonal antibody (trastuzumab) is used as ligand for the targeting the drug bearing carriers to BC. Thus, trastuzumab anchored pH-sensitive liposomes bearing PTX and ELA were developed using thin film hydration method and Box-Behnken Design (BBD) for optimizing various formulation variables. The optimized liposomes undergo characterization such as vesicle size, PDI, and zeta potential, which were observed to be 122 ± 2.14 nm, 0.224, and -15.5 mV for PEGylated pH-sensitive liposomes (PEG-Ls) and 134 ± 1.88 nm, 0.238, and -13.98 mV for TPPLs, respectively. The results of the in vitro drug release study of both formulations (PEG-Ls and TPPLs) showed enhanced percentage drug release at an acidic pH 5 as compared to drug release at a physiological pH 7.4. Further, the in vitro cytotoxicity studies were performed in the SK-BR-3 and MDA-MB-231 cell lines. The cellular uptake study of FITC-loaded TPPLs in SK-BR-3 cells showed greater uptake than FITC-loaded PEG-Ls, while in MDA-MB-231 cells there was no significant difference in cell uptake between FITC-loaded TPPLs and FITC-loaded PEG-Ls. Hence, it can be concluded that the HER-2 overexpressing cancer cell line (SK-BR-3) was showed better cytotoxicity and cell uptake of TPPLs than the cells that expressed low levels of HER2 (MDA-MB-231). The in vivo tumor regression study, TPPLs showed significantly more tumor burden reduction i.e. up ∼74% as compared to other liposomes after 28 days. Furthermore, the in vivo studies of TPPLs showed a minimal toxicity profile, minimal hemolysis, higher tumor tissue distribution, and superior antitumor efficacy as compared to other formulations. These studies confirmed that TPPLs are a safe and efficacious treatment for breast cancer.

Opportunities in combinational chemo-immunotherapy for breast cancer using nanotechnology: an emerging landscape.

INTRODUCTION: Breast carcinoma (BC) is one of the most frequent causes of cancer-related death among women, which is due to the poor response to conventional therapy. There are several complications associated with monotherapy for cancer, such as cytotoxicity to normal cells, multidrug resistance (MDR), side effects, and limited applications. To overcome these challenges, a combination of chemotherapy and immunotherapy (monoclonal antibodies, anticancer vaccines, checkpoint inhibitors, and cytokines) has been introduced. Drug delivery systems (DDSs) based on nanotechnology have more applications in BC treatment owing to their controlled and targeted drug release with lower toxicity and reduced adverse drug effects. Several nanocarriers, such as liposomes, nanoparticles, dendrimers, and micelles, have been used for the effective delivery of drugs. AREAS COVERED: This article presents opportunities and challenges in BC treatment, the rationale for cancer immunotherapy, and several combinational approaches with their applications for BC treatment. EXPERT OPINION: Nanotechnology can be used for the early prognosis and cure of BC. Several novel and targeted DDSs have been developed to enhance the efficacy of anticancer drugs. This article aims to understand new strategies for the treatment of BC and the appropriate design of nanocarriers used as a combinational DDS.

Novel Strategies for Targeting Prostate Cancer.

Prostate cancer (PCa) is a worldwide issue, with a rapid increase in its occurrence and mortality. Over the years, various strategies have been implemented to overcome the hurdles that exist in the treatment of PCa. Consistently, there is a change in opinion about the methodologies in clinical trial that have engrossed towards the treatment of PCa. Currently, there is a need to resolve these newly recognized challenges by developing newer rational targeting systems. The ongoing clinical protocol for the therapy using different targeting systems is undertaken followed by local targeting to cancer site. A number of new drug targeting systems like liposomes, nanoemulsions, magnetic nanoparticles (MNPs), solid lipid nanoparticles, drug-peptide conjugate systems, drug-antibody conjugate systems, epigenetic and gene therapy approaches, and therapeutic aptamers are being developed to suit this protocol. Recent advancements in the treatment of PCa with various nanocarriers have been reported with respect to newly identified biological barriers and intended to solve the contexts. This review encompasses the input of nanotechnology in particular targeting of PCa which might escape the lifethreatening side effects and potentially contribute to bring fruitful clinical outcomes.

Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment.

A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0.04, +23.4 ± 0.3 mV and 88.3 ± 0.2% (PTX), and 89.6 ± 0.5% (DOX) respectively. In vitro drug release study of optimized formulation was carried out using dialysis tube method. FA-conjugated PTX-DOX-loaded NLCs showed 75.6 and 78.4% (cumulative drug release) of PTX and DOX respectively in 72 h in PBS (pH 7.4)/methanol (7:3), while in the case of FA-conjugated PTX-DOX-loaded NLCs, cumulative drug release recorded was 80.4 and 82.8% of PTX and DOX respectively in 72 h in PBS (pH 4.0)/methanol (7:3). Further, the formulation(s) were evaluated for ex vivo cytotoxicity study. The cytotoxicity assay in doxorubicin-resistant human breast cancer MCF-7/ADR cell lines revealed lowest GI50 value of FA-D-P NLCs which was 1.04 ± 0.012 µg/ml, followed by D-P NLCs and D-P solution with GI50 values of 3.12 ± 0.023 and 3.89 ± 0.007 µg/ml, respectively. Findings indicated that the folic acid-conjugated PTX and DOX co-loaded NLCs exhibited lower GI50 values as compared to unconjugated PTX and DOX co-loaded NLCs; thus, they have relatively potential anticancer efficacy against resistant tumor.