Exploring nanocarriers as innovative materials for advanced drug delivery strategies in onco-immunotherapies.

In recent years, Onco-immunotherapies (OIMTs) have been shown to be a potential therapy option for cancer. Several immunotherapies have received regulatory approval, while many others are now undergoing clinical testing or are in the early stages of development. Despite this progress, a large number of challenges to the broad use of immunotherapies to treat cancer persists. To make immunotherapy more useful as a treatment while reducing its potentially harmful side effects, we need to know more about how to improve response rates to different types of immunotherapies. Nanocarriers (NCs) have the potential to harness immunotherapies efficiently, enhance the efficiency of these treatments, and reduce the severe adverse reactions that are associated with them. This article discusses the necessity to incorporate nanomedicines in OIMTs and the challenges we confront with current anti-OIMT approaches. In addition, it examines the most important considerations for building nanomedicines for OIMT, which may improve upon current immunotherapy methods. Finally, it highlights the applications and future scenarios of using nanotechnology.

Dacarbazine-primed carbon quantum dots coated with breast cancer cell-derived exosomes for improved breast cancer therapy.

Imprecise targeting of chemotherapeutic drugs often leads to severe toxicity during breast cancer therapy. To address this issue, we have devised a strategy to load dacarbazine (DC) into fucose-based carbon quantum dots (CQDs), which are subsequently coated with exosomes (Ex-DC@CQDs) derived from breast cancer cells. Nanoparticle tracking analysis and western blotting revealed that Ex-DC@CQDs retained the structural and functional characteristics of exosomes. We found that exosomes facilitated the transport of DC@CQDs to cancer cells via heparan sulfate proteoglycan (HSPG) receptors, followed by an augmented depolarization of the mitochondrial membrane potential, ROS generation, and induction of apoptosis leading to cell death. In vivo imaging and pharmacokinetic studies demonstrated enhanced antitumor targeting and efficacy compared to free DC which we attribute to an improved pharmacokinetic profile, a greater tumor accumulation via exosome-mediated- HSPG receptor-driven cell uptake, and sustained release of the Ex-DC@CQDs. Our findings may pave the way for the further development of biologically sourced nanocarriers for breast cancer targeting.

Immobilized doxorubicin and ribociclib carbamate linkers encaged in surface modified cubosomes spatially target tumor reductive environment to enhance antitumor efficacy.

In the present investigation, we have strategically synthesized Glutathione (GSH) stimuli-sensitive analogues using carbamate linkers (CL) of DOX (DOX-CL) and RB (RB-CL) which were then anchored to gold nanoparticles (Au-DOX-CL, Au-RB-CL) using mPEG as a spacer. It was observed that carbamate linkage (CL) with four carbon spacer is critical, to position the terminal thiol group, to access the carbamate group efficiently to achieve GSH-assisted release of DOX and RB in tumor-specific environment. When assessed for GSH reductase activity in MDA-MB 231 cell lines, Au-DOX-CL and Au-RB-CL showed nearly 4.18 and 3.13 fold higher GSH reductive activity as compared to the control group respectively. To achieve spatial tumor targeting with a high payload of DOX and RB, Au-DOX-CL and Au-RB-CL were encapsulated in the cell-penetrating peptide (CPP) modified liquid crystalline cubosomes i.e. CPP-Cu(Au@CL-DR). After internalization, the prototype nanocarriers release respective drugs at a precise GSH concentration inside the tumor tissues, amplifying drug concentration to a tune of five-fold. The drug concentrations remain within the therapeutic window for 72 h with a significant reduction of RB (7.8-fold) and DOX (6-fold) concentrations in vital organs, rendering reduced toxicity and improved survival. Overall, this constitutes a promising chemotherapeutic strategy against cancer and its potential application in the offing.

Hyaluronic acid-engineered Bcl-2 inhibitor nanocrystals for site-specific delivery to breast tumor cells.

Aim: This investigation aims to repurpose venetoclax using hyaluronic acid-coated venetoclax nanocrystals (HA-VEN-NCs) to target breast cancer. Materials & methods: An antisolvent precipitation method was used to fabricate the nanocrystals and optimize them using central composite design. Hyaluronic acid (HA)-coated and -uncoated nanocrystals were compared in terms of in vitro drug release, cell line studies, CD44-expressing breast tumor cell binding capability and anticancer activity. Results: HA-VEN-NCs and venetoclax nanocrystals (VEN-NCs) showed pH-responsive drug-release behavior, exhibiting sustained release at pH 6.8. Our extensive in vitro cell line investigation showed that HA-VEN-NCs efficiently bind to CD44-expressing breast tumor cells and possess excellent anticancer activity (IC50: 2.00 µg/ml) compared with VEN-NCs. Conclusion: Our findings anticipate that HA-VEN-NCs could serve as valuable nanoplatforms for cancer treatments in the future.

Recent updates on innovative approaches to overcome drug resistance for better outcomes in cancer.

The multi-dimensional challenge of drug resistance is one of the pivotal hindrances for cancer chemotherapy. A reductive approach to define and distinguish the main aspects of drug resistance, such as tumor growth kinetics about tumor micro-environment (tumor multifariousness), therapeutic pressure, physical barricades, irreversible genetic mutation, as well as role of the immune system, are the main causes of failure in cancer therapy are presented systematically. We are focusing on general approaches to reduce drug resistance: earlier diagnosis of tumors allowing for cancer halting; dynamic surveillance throughout treatment; the adding of new therapeutic strategies and improve pharmacodynamics precepts resulting in profound effects; and identification of cancerous cells repositories using high-throughput monitoring, as well as the interoperability of clinical- gene mapping statics are described in detail. These strategies could be potentially constructed for any tumor at any precise moment and used to guide therapy selection. Chemotherapeutic agents results in mild improved survival in clinical trials owing to several pathophysiologic obstacles, such as intra-tumoral dispersion, invasion & intra-cellular transportation. This review highlights recent advancements in developing new therapeutic innovations to combat drug resistance in cancer therapy by overcoming various barricades in the tumor microenvironment.

Critical parameters for design and development of multivalent nanoconstructs: recent trends.

A century ago, the groundbreaking concept of the magic bullet was given by Paul Ehrlich. Since then, this concept has been extensively explored in various forms to date. The concept of multivalency is among such advancements of the magic bullet concept. Biologically, the concept of multivalency plays a critical role in significantly huge numbers of biochemical interactions. This concept is the sole reason behind the higher affinity of biological molecules like viruses to more selectively target the host cell surface receptors. Multivalent nanoconstructs are a promising approach for drug delivery by the active targeting principle. Designing and developing effective and target-specific multivalent drug delivery nanoconstructs, on the other hand, remain a challenge. The underlying reason for this is a lack of understanding of the crucial interactions between ligands and cell surface receptors, as well as the design of nanoconstructs. This review highlights the need for a better theoretical understanding of the multivalent effect of what happens to the receptor-ligand complex after it has been established. Furthermore, the critical parameters for designing and developing robust multivalent systems have been emphasized. We have also discussed current advances in the design and development of multivalent nanoconstructs for drug delivery. We believe that a thorough knowledge of theoretical concepts and experimental methodologies may transform a brilliant idea into clinical translation.

COVID-19 Infection: Targeting Possibilities for Treatment.

The outbreak of novel coronavirus (nCoV) or severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in December 2019 in Wuhan, China, has posed an international public health emergency worldwide and forced people to be confined in their homes. This virus is of high-risk category and is declared a pandemic by the World Health Organization (WHO). The worldwide researchers and various health professionals are working together to determine the best way to stop its spread or halt this virus's spread and circumvent this pandemic condition threatening millions of human lives. The absence of definitive treatment is possible to explore to reduce virus infection and enhance patient recovery. Along with off-label medicines, plasma therapy, vaccines, the researchers exploit the various plants/herbs and their constituents to effectively treat nCoV infection. The present study aimed to present brief and most informative salient features of the numerous facts regarding the SARS-CoV-2, including the structure, genomic sequence, recent mutation, targeting possibility, and various hurdles in research progress, and off-labeled drugs, convalescent plasma therapy, vaccine and plants/herbs for the treatment of coronavirus disease-2019 (COVID-19). Results showed that off-labeled drugs such as hydroxychloroquine, dexamethasone, tocilizumab, antiviral drug (remdesivir, favipiravir), etc., give positive results and approved for use or approved for restricted use in some countries like India. Future research should focus on these possibilities that may allow the development of an effective treatment for COVID-19.