No abstract

Modern oncotherapy approaches are based on inducing controlled apoptosis in tumor cells. Although a number of apoptosis-induction approaches are available, site-specific delivery of therapeutic agents still remain the biggest hurdle in achieving the desired cancer treatment benefit. Additionally, systemic treatment-induced toxicity remains a major limiting factor in chemotherapy. To specifically address drug-accessibility and chemotherapy side effects, oncolytic virotherapy (OV) has emerged as a novel cancer treatment alternative. In OV, recombinant viruses with higher replication capacity and stronger lytic properties are being considered for tumor cell-targeting and subsequent cell lysing. Successful application of OVs lies in achieving strict tumor-specific tropism called oncotropism, which is contingent upon the biophysical interactions of tumor cell surface receptors with viral receptors and subsequent replication of oncolytic viruses in cancer cells. In this direction, few viral vector platforms have been developed and some of these have entered pre-clinical/clinical trials. Among these, the Vesicular stomatitis virus (VSV)-based platform shows high promise, as it is not pathogenic to humans. Further, modern molecular biology techniques such as reverse genetics tools have favorably advanced this field by creating efficient recombinant VSVs for OV; some have entered into clinical trials. In this review, we discuss the current status of VSV based oncotherapy, challenges, and future perspectives regarding its therapeutic applications in the cancer treatment.

The ultimate aim in developing controlled drug delivery systems is to derive formulations to achieve drug release at a constant rate over a long duration. The drug release profile that follows zero-order kinetics is crucial for reduction in the drug administration frequency, reduced cytotoxicity, and improved convenience and compliance of patients. Designed drug delivery systems for achieving zero-order release are often complex, expensive, and difficult to manufacture. Herein, we demonstrate that a supramolecular hydrogel formed through the self-assembly of guanosine monophosphate (GMP) into highly ordered G-quadruplex structure and cross-linked through Fe3+ and Ca2+ ions exhibits potential for the pH-responsive controlled zero-order drug release of doxorubicin, a model chemotherapeutic drug. The fibril formation is initiated by the self-assembly of GMP into a quadruplex complex, which is cross-linked through the complexation of the phosphate groups with Fe­(III) ions, resulting in a spontaneous hydrogel formation. The Ca2+ ions facilitate the improvement in the mechanical integrity of the fibril network in the Fe-GMP hydrogel via cross-linking of sugar moieties. The hydrogel showed a high loading capacity for drug molecules and a pH-responsive sustained zero-order drug release over several days owing to the lowered degradability of the cross-linked hydrogel in acidic buffer stimulant. In vitro drug-release studies further established a controlled pH-triggered drug release profile. The Ca2+ cross-linking of the Fe-GMP hydrogel also resulted in significant enhancement in the biocompatibility of the drug delivery system. The fabrication of biocompatible, low-cost, and efficient Ca2+ cross-linked metal–organic hydrogels may present promising applications in biological fields.

Outfitted with numerous coordination and hydrogen bonding sites, nucleotides represent a class of naturally occurring ligands for coordination with metals leading to both hard and soft materials for a wide range of applications. Reported herein, a new multistimuli-responsive metal–organic hydrogel through the spontaneous self-associative complexation of inosine 5′-monophosphate (IMP) with Ag­(I) ions in aqueous medium. The strong and optically transparent hydrogels were formed without the aid of any external influences such as heating/cooling cycles or ultrasonication and comprise of an interconnected matrix of nanofilaments constructed from helically stacked, chiral arrays of Ag-IMP dimers. The metallogel exhibits diverse properties including self-healing, stimuli-responsiveness, transparency, and injectibility. The direct gelation specificity to Ag (I) ions is highly phase selective only to water, and the ability of the freeze-dried xerogel to gel water is exploited for the separation of water from various organic solvents. Further, the Ag-IMP hydrogel exhibits efficient antibacterial activity against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) bacteria. Ag nanoparticles could be generated in situ without disrupting the hydrogel network through photoreduction by light. The robustness and multidimensional applicability combined with ease of synthesis make this coordination driven hydrogel a prospective material for environmental and biomedical applications.

Indocyanine green (ICG) is a clinically approved near-infrared (NIR) contrast agent used in medical diagnosis. However, ICG has not been used to its fullest for biomedical imaging applications due to its low fluorescence quantum yield, aqueous instability, concentration-dependent aggregation, and photo and thermal degradations, leading to quenching of its fluorescence emission. In the present study, a nanosized niosomal formulation, ICGNiosomes (ICGNios), is fabricated to encapsulate and protect ICG from degradation. Interestingly, compared to free ICG, the ICGNios exhibited higher fluorescence quantum yield and fluorescence emission with a bathochromic shift. Also, ICGNios nanoparticles are biocompatible, biodegradable, and readily uptaken by the cells. Furthermore, ICGNios show more enhanced fluorescence intensity through ∼1 cm thick chicken breast tissue compared to free ICG, which showed minimal emission through the same thickness of tissue. Our results suggest that ICGNios could offer a promising platform for deep-tissue NIR in vivo imaging to visualize inaccessible tissue microstructures for disease diagnosis and therapeutics.