Recent advancements in nanomaterial-mediated ferroptosis-induced cancer therapy: Importance of molecular dynamics and novel strategies.

Ferroptosis is a novel type of controlled cell death resulting from an imbalance between oxidative harm and protective mechanisms, demonstrating significant potential in combating cancer. It differs from other forms of cell death, such as apoptosis and necrosis. Molecular therapeutics have hard time playing the long-acting role of ferroptosis induction due to their limited water solubility, low cell targeting capacity, and quick metabolism in vivo. To this end, small molecule inducers based on biological factors have long been used as strategy to induce cell death. Research into ferroptosis and advancements in nanotechnology have led to the discovery that nanomaterials are superior to biological medications in triggering ferroptosis. Nanomaterials derived from iron can enhance ferroptosis induction by directly releasing large quantities of iron and increasing cell ROS levels. Moreover, utilizing nanomaterials to promote programmed cell death minimizes the probability of unfavorable effects induced by mutations in cancer-associated genes such as RAS and TP53. Taken together, this review summarizes the molecular mechanisms involved in ferroptosis along with the classification of ferroptosis induction. It also emphasized the importance of cell organelles in the control of ferroptosis in cancer therapy. The nanomaterials that trigger ferroptosis are categorized and explained. Iron-based and noniron-based nanomaterials with their characterization at the molecular and cellular levels have been explored, which will be useful for inducing ferroptosis that leads to reduced tumor growth. Within this framework, we offer a synopsis, which traverses the well-established mechanism of ferroptosis and offers practical suggestions for the design and therapeutic use of nanomaterials.

Unlocking the potential of nanocarrier-mediated mRNA delivery across diverse biomedical frontiers: A comprehensive review.

Messenger RNA (mRNA) has gained marvelous attention for managing and preventing various conditions like cancer, Alzheimer's, infectious diseases, etc. Due to the quick development and success of the COVID-19 mRNA-based vaccines, mRNA has recently grown in prominence. A lot of products are in clinical trials and some are already FDA-approved. However, still improvements in line of optimizing stability and delivery, reducing immunogenicity, increasing efficiency, expanding therapeutic applications, scalability and manufacturing, and long-term safety monitoring are needed. The delivery of mRNA via a nanocarrier system gives a synergistic outcome for managing chronic and complicated conditions. The modified nanocarrier-loaded mRNA has excellent potential as a therapeutic strategy. This emerging platform covers a wide range of diseases, recently, several clinical studies are ongoing and numerous publications are coming out every year. Still, many unexplained physical, biological, and technical problems of mRNA for safer human consumption. These complications were addressed with various nanocarrier formulations. This review systematically summarizes the solved problems and applications of nanocarrier-based mRNA delivery. The modified nanocarrier mRNA meaningfully improved mRNA stability and abridged its immunogenicity issues. Furthermore, several strategies were discussed that can be an effective solution in the future for managing complicated diseases.

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.

Long-acting formulation strategies for protein and peptide delivery in the treatment of PSED.

The invigoration of protein and peptides in serious eye disease includes age-related macular degeneration, choroidal neovascularization, retinal neovascularization, and diabetic retinopathy. The transportation of macromolecules like aptamers, recombinant proteins, and monoclonal antibodies to the posterior segment of the eye is challenging due to their high molecular weight, rapid degradation, and low solubility. Moreover, it requires frequent administration for prolonged therapy. The long-acting novel formulation strategies are helpful to overcome these issues and provide superior therapy. It avoids frequent administration, improves stability, high retention time, and avoids burst release. This review briefly enlightens posterior segments of eye diseases with their diagnosis techniques and treatments. This article mainly focuses on recent advanced approaches like intravitreal implants and injectables, electrospun injectables, 3D printed drug-loaded implants, nanostructure thin-film polymer devices encapsulated cell technology-based intravitreal implants, injectable and depots, microneedles, PDS with ranibizumab, polymer nanoparticles, inorganic nanoparticles, hydrogels and microparticles for delivering macromolecules in the eye for intended therapy. Furthermore, novel techniques like aptamer, small Interference RNA, and stem cell therapy were also discussed. It is predicted that these systems will make revolutionary changes in treating posterior segment eye diseases in future.

Stimuli responsive and receptor targeted iron oxide based nanoplatforms for multimodal therapy and imaging of cancer: Conjugation chemistry and alternative therapeutic strategies.

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Hot-Melt Extrusion: An Emerging Technique for Solubility Enhancement of Poorly Water-Soluble Drugs.

The solubility of the drug is a significant aspect to be considered during manufacturing of pharmaceutical products. Poor aqueous solubility of drugs imparts depleted bioavailability. In this regard, several techniques are available for enhancing drug solubility or dissolution. However, only few of them are scalable and industrially applicable. Hot-melt extrusion (HME) is one such technique that has been widely used in the industry. It is a single-step, continuous manufacturing, and scalable method that has proved successful in improving the solubility of poorly soluble drugs. This review highlights the numerous pharmaceutical applications of HME, such as formulations of sterile implants, taste masking of unpleasant drugs, cocrystallization, salt formation, sustained and controlled release formulations, etc. It also describes various hydrophilic and hydrophobic carriers utilized in HME. This review also briefly discusses the recent advances in HME and gives an update on the currently available marketed products. The opportunities and challenges in future development of pharmaceutical products by HME technique are also discussed.

Molybdenum-based hetero-nanocomposites for cancer therapy, diagnosis and biosensing application: Current advancement and future breakthroughs.

In recent years, there have been significant advancements in the nanotechnology for cancer therapy. Even though molybdenum disulphide (MoS2)-based nanocomposites demonstrated extensive applications in biosensing, bioimaging, phototherapy, the review article focusing on MoS2 nanocomposite platform has not been accounted for yet. The review summarizes recent strategies on design and fabrication of MoS2-based nanocomposites and their modulated properties in cancer treatment. The review also discussed several therapeutic strategies (photothermal, photodynamic, immunotherapy, gene therapy and chemotherapy) and their combinations for efficient cancer therapy along with certain case studies. The review also inculcates various diagnostic techniques viz. magnetic resonance imaging, computed tomography, photoacoustic imaging and fluorescence imaging for diagnosis of cancer.

A key role by polymers in microneedle technology: a new era.

The skin serves as the major organ in the targeted transdermal drug delivery system for many compounds. The microneedle acts as a novel technique to deliver drugs across the different layers of the skin, including the major barrier stratum corneum, in an effective manner. A microneedle array patch comprises dozens to hundreds of micron-sized needles with numerous structures and advantages resulting from their special and smart designs. The microneedle approach is much more advanced than conventional transdermal delivery pathways due to several benefits like minimally invasive, painless, self-administrable, and enhanced patient compliance. The microneedles are classified into hollow, solid, coated, dissolving, and hydrogel. Several polymers are used to fabricate microneedle, such as natural, semi-synthetic, synthetic, biodegradable, and swellable polymers. Researchers in the preparation of microneedles also explored the combinations of polymers. The safety of the polymer used in microneedle is a crucial aspect to prevent toxicity in vivo. Thus, this review aims to provide a detailed review of microneedles and mainly focus on the various polymers used in the fabrication of microneedles.