Cancer is a serious threat to human health because of its high annual mortality rate. It has attracted significant attention in healthcare, and identifying effective strategies for the treatment and relief of cancer pain requires urgency. Drug delivery systems (DDSs) offer the advantages of excellent efficacy, low cost, and low toxicity for targeting drugs to tumor sites. In recent decades, copolymer carriers based on poly(phenylalanine) (PPhe) and poly(3,4-dihydroxy-L-phenylalanine) (PDopa) have been extensively investigated owing to their good biocompatibility, biodegradability, and controllable stimulus responsiveness, which have resulted in DDSs with loading and targeted delivery capabilities. In this review, we introduce the synthesis of PPhe and PDopa, highlighting the latest proposed synthetic routes and comparing the differences in drug delivery between PPhe and PDopa. Subsequently, we summarize the various applications of PPhe and PDopa in nanoscale-targeted DDSs, providing a comprehensive analysis of the drug release behavior based on different stimulus-responsive carriers using these two materials. In the end, we discuss the challenges and prospects of polypeptide-based DDSs in the field of cancer therapy, aiming to promote their further development to meet the growing demands for treatment.

Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease\'s progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA\'s inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Messenger RNA (mRNA) has emerged as a promising therapeutic molecule with numerous clinical applications in treating central nervous system disorders, tumors, COVID-19, and other diseases. mRNA therapies must be encapsulated into safe, stable, and effective delivery vehicles to preserve the cargo from degradation and prevent immunogenicity. Exosomes have gained growing attention in mRNA delivery because of their good biocompatibility, low immunogenicity, small size, unique capacity to traverse physiological barriers, and cell-specific tropism. Moreover, these exosomes can be engineered to utilize the natural carriers to target specific cells or tissues. This targeted approach will enhance the efficacy and reduce the side effects of mRNAs. However, difficulties such as a lack of consistent and reliable methods for exosome purification and the efficient encapsulation of large mRNAs into exosomes must be addressed. This article outlines current breakthroughs in cell-derived vesicle-mediated mRNA delivery and its biomedical applications.

Naturally generated lipid nanoparticles termed extracellular vesicles (EVs) hold significant promise as engineerable therapeutic delivery vehicles. However, active loading of protein cargo into EVs in a manner that is useful for delivery remains a challenge. Here, we demonstrate that by rationally designing proteins to traffic to the plasma membrane and associate with lipid rafts, we can enhance loading of protein cargo into EVs for a set of structurally diverse transmembrane and peripheral membrane proteins. We then demonstrate the capacity of select lipid tags to mediate increased EV loading and functional delivery of an engineered transcription factor to modulate gene expression in target cells. We envision that this technology could be leveraged to develop new EV-based therapeutics that deliver a wide array of macromolecular cargo.

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).

BACKGROUND: Neglected Tropical Diseases (NTD) are chronic infectious conditions that primarily affect marginalized populations. The chemotherapeutic arsenal available for treating NTD is limited and outdated, which poses a challenge in controlling and eradicating these diseases. This is exacerbated by the pharmaceutical industry\'s lack of interest in funding the development of new therapeutic alternatives. In addition, a considerable number of drugs used in NTD therapy have low aqueous solubility. To address this issue, solubility enhancement strategies, such as the use of inclusion complexes with cyclodextrins (CD) can be employed.
OBJECTIVE: Therefore, this systematic review aims to present the application of CD in complexing with drugs and chemotherapeutic compounds used in the therapy of some of the most prevalent NTD worldwide and how these complexes can enhance the treatment of these diseases.
METHODS: Two bibliographic databases, Science Direct and PubMed, were used to conduct the search. The selection of studies and the writing of this systematic review followed the criteria outlined by the PRISMA guidelines.
RESULTS: From a total of 978 articles, 23 were selected after applying the exclusion criteria. All the studies selected were consistent with the use of CD as a strategy to increase the solubility of therapeutic agents used in NTD.
CONCLUSIONS: The results indicate that CD can enhance the solubility of chemotherapeutic agents for the treatment of Neglected Tropical Diseases (NTD). This review presents data that clearly highlights the potential use of CD in the development of new treatments for neglected tropical diseases. It can assist in the formulation of future treatments that are more effective and safer.

Globally, non‑small cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by pre‑preparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDP‑loaded PNA‑modified liposomes (CDDP‑PNA‑Lip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDP‑PNA‑Lip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted anti‑tumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)‑loaded PNA‑modified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDP‑PNA‑Lip resulted in a 2.65‑fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligand‑modified liposomes may significantly improve its tumour‑targeting capabilities, providing valuable insights for clinical drug development.

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.

Benign prostatic hyperplasia and prostate cancer are often associated with lower urinary tract symptoms, which can severely affect patient quality of life. To address this challenge, we developed and optimized an injectable compound, prostate ablation and drug delivery agent (PADA), for percutaneous prostate tissue ablation and concurrently delivered therapeutic agents. PADA is an ionic liquid composed of choline and geranic acid mixed with anticancer therapeutics and a contrast agent. The PADA formulation was optimized for mechanical properties compatible with hand injection, diffusion capability, cytotoxicity against prostate cells, and visibility of an x-ray contrast agent. PADA also exhibited antibacterial properties against highly resistant clinically isolated bacteria in vitro. Ultrasound-guided injection, dispersion of PADA in the tissue, and tissue ablation were tested ex vivo in healthy porcine, canine, and human prostates and in freshly resected human tumors. In vivo testing was conducted in a murine subcutaneous tumor model and in the canine prostate. In all models, PADA decreased the number of viable cells in the region of dispersion and supported the delivery of nivolumab throughout a portion of the tissue. In canine survival experiments, there were no adverse events and no impact on urination. The injection approach was easy to perform under ultrasound guidance and produced a localized effect with a favorable safety profile. These findings suggest that PADA is a promising therapeutic prostate ablation strategy to treat lower urinary tract symptoms.