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Abstract Chemotherapy persists as the primary intervention for breast cancer, with chemoresistance posing the principal obstacle to successful treatment. Herein, we show that cartilage oligomeric matrix protein (COMP) expression leads to increased cancer cell survival and attenuated apoptosis under treatment with several chemotherapeutic drugs, anti-HER2 targeted treatment, and endocrine therapy in several breast cancer cell lines tested. The COMP-induced chemoresistance was independent of the breast cancer subtype. Extracellularly delivered recombinant COMP failed to rescue cells from apoptosis while endoplasmic reticulum (ER)-restricted COMP-KDEL conferred resistance to apoptosis, consistent with the localization of COMP in the ER, where it interacted with calpain. Calpain activation was reduced in COMP-expressing cells and maintained at a lower level of activation during treatment with epirubicin. Moreover, the downstream caspases of calpain, caspases -9, -7, and -3, exhibited significantly reduced activation in COMP-expressing cells under chemotherapy treatment. Chemotherapy, when combined with calpain activators, rendered the cells expressing COMP more chemosensitive. Also, the anti-apoptotic proteins phospho-Bcl2 and survivin were increased in COMP-expressing cells upon chemotherapy. Cells expressing a mutant COMP lacking thrombospondin repeats exhibited reduced chemoresistance compared to cells expressing full-length COMP. Evaluation of calcium levels in the ER, cytosol, and mitochondria revealed that COMP expression modulates intracellular calcium homeostasis. Furthermore, patients undergoing chemotherapy or endocrine therapy demonstrated significantly reduced overall survival time when tumors expressed high levels of COMP. This study identifies a novel role of COMP in chemoresistance and calpain inactivation in breast cancer, a discovery with potential implications for anti-cancer therapy.

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity. Currently, gene therapy drugs such as siRNA, shRNA, antisense oligonucleotide, CRISPR/Cas9 system, plasmid DNA and miRNA have shown great potential in biomedical applications. To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues, cells and organelles, the development of excellent drug delivery vehicles is of utmost importance. Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression. With the development of nanotechnology, novel nanocarriers are gradually replacing viral vectors, emerging superior performance. This review mainly illuminates the current widely used gene therapy drugs, summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs, and sums up the application of gene therapy to treat genetic diseases. Additionally, the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system. [ABSTRACT FROM AUTHOR]

Introduction: As a protein-based biomaterial for potential cancer targeting delivery, apoferritin has recently attracted interest.Areas covered: In this review, we discuss the development of this cage-like protein as an endogenous nanocarrier that can hold molecules in its cavity. We present the specific characterizations and formulations of apoferritin nanocarriers, and outline the recent progress of the protein as an appropriate tumor-delivery vehicle in different therapeutic strategies to treat solid tumors. Finally, we propose how the application for cancer drug repurposing delivery within apoferritin could expand cancer treatment in the future.Expert opinion: Being a ubiquitous iron storage protein that exists in many living organisms, apoferritin is promising as a cancer tumor-targeting nanocarrier. By exploiting its versatility, apoferritin could be used for cancer repurposed drug delivery and could reduce the high cost of new drug discovery development and shorten the formulation process. [ABSTRACT FROM AUTHOR]

Solidification of self-microemulsifying drug delivery systems (SMEDDS) is one of the major trends to promote the transformation of self-microemulsion technology into industrialization. Here, a preliminary curcumin SMEDDS formulation was constructed to improve the druggability of curcumin, through the determination of equilibrium solubility determination, self-emulsifying grading assessment, and pseudo-ternary phase diagrams drafting. Furthermore, the optimal curcumin SMEDDS formulation consisted of 10% Ethyl oleate, 57.82% Cremophor RH 40, and 32.18% Transcutol P was obtained by the simplex lattice design. Besides, curcumin solid self-microemulsifying drug delivery system (S-SMEDDS) was developed by the extrusion and spheronization process to achieve the solidification of SMEDDS. The formulation of curcumin S-SMEDDS pellets was screened by the single factor experiment and the process parameters were investigated using the orthogonal optimization method. Subsequently, curcumin S-SMEDDS pellets were evaluated by apparent morphology characterization, redispersibility study, drug release behavior, and pharmacokinetic evaluation. Results from the pharmacokinetic study in rabbits showed that the AUC0–τ of the curcumin S-SMEDDS pellets and curcumin suspension were 5.91 ± 0.28 µg/mL·h and 2.05 ± 0.04 µg/mL·h, while the relative bioavailability was 289.30%. These studies demonstrated that S-SMEDDS pellets can be a promising strategy for curcumin industrialized outputs. [ABSTRACT FROM AUTHOR]

Glaucoma is considered a leading cause of blindness with the human eye being one of the body's most delicate organs. Ocular diseases encompass diverse diseases affecting the anterior and posterior ocular sections, respectively. The human eye's peculiar and exclusive anatomy and physiology continue to pose a significant obstacle to researchers and pharmacologists in the provision of efficient drug delivery. Though several traditional invasive and noninvasive eye therapies exist, including implants, eye drops, and injections, there are still significant complications that arise which may either be their low bioavailability or the grave ocular adverse effects experienced thereafter. On the other hand, new nanoscience technology and nanotechnology serve as a novel approach in ocular disease treatment. In order to interact specifically with ocular tissues and overcome ocular challenges, numerous active molecules have been modified to react with nanocarriers. In the general population of glaucoma patients, disease growth and advancement cannot be contained by decreasing intraocular pressure (IOP), hence a spiking in future research for novel drug delivery systems and target therapeutics. This review focuses on nanotechnology and its therapeutic and diagnostic prospects in ophthalmology, specifically glaucoma. Nanotechnology and nanomedicine history, the human eye anatomy, research frontiers in nanomedicine and nanotechnology, its imaging modal quality, diagnostic and surgical approach, and its possible application in glaucoma will all be further explored below. Particular focus will be on the efficiency and safety of this new therapy and its advances. [ABSTRACT FROM AUTHOR]

One of the most encountered obstacles for utilizing nano-sized vehicles to implement the in vivo delivery of nucleic acid drugs (NADs) is the possible steric hindrance caused by their intrinsic size and charge. In this work, we added Ca2+ for the pH triggered self-assembly process of H-apoferritin (HFn), to neutralize negative charges and help siRNA condense during complexation and particle formation. As expected, the internalization efficiency of siRNA in HFn particle formation could be enhanced 1.65-fold, compared with that without incorporated Ca2+. Furthermore, the calcification that occurred within the cavity of HFn particles endows them with endosomal escape capability, which could explain their contribution to the demonstrated in vitro and in vivo gene silencing effect achieved by the internalized siRNA. Thus, this Ca2+ participating self-assembly process of a protein nanostructure would lead to advanced internalization efficiency for NAD therapy.