Cancer immunotherapy has veered the paradigm of cancer treatment. Despite recent advances in immunotherapy for improved antitumor efficacy, the complicated tumor microenvironment (TME) is highly immunosuppressive, yielding both astounding and unsatisfactory clinical successes. In this regard, clinical outcomes of currently available immunotherapy are confined to the varied immune systems owing in large part to the lack of understanding of the complexity and diversity of the immune context of the TME. Various advanced designs of nanomedicines could still not fully surmount the delivery barriers of the TME. The immunosuppressive TME may even dampen the efficacy of antitumor immunity. Recently, some nanotechnology-related strategies have been inaugurated to modulate the immunosuppressive cells within the tumor immune microenvironment (TIME) for robust immunotherapeutic responses. In this review, we will highlight the current understanding of the immunosuppressive TIME and identify disparate subclasses of TIME that possess an impact on immunotherapy, especially those unique classes associated with the immunosuppressive effect. The immunoregulatory cell types inside the immunosuppressive TIME will be delineated along with the existing and potential approaches for immunosuppressive cell modulation. After introducing the various strategies, we will ultimately outline both the novel therapeutic targets and the potential issues that affect the efficacy of TIME-based nanomedicines.

The development of biomimetic drug delivery systems for biomedical applications has attracted significant research attention. As the use of cell membrane as a surface coating has shown to be a promising platform for several disease treatments. Cell-membrane-coated nanoparticles exhibit enhanced immunocompatibility and prolonged circulation time. Herein, human red blood cell (RBC) membrane-cloaked nanoparticles with enhanced targeting functionality were designed as a targeted nanotheranostic against cancer. Naturally, derived human RBC membrane modified with targeting ligands coated onto polymeric nanoparticle cores containing both chemotherapy and imaging agent. Using epithelial cell adhesion molecule (EpCAM)-positive MCF-7 breast cancer cells as a disease model, the nature-inspired targeted theranostic human red blood cell membrane-coated polymeric nanoparticles (TT-RBC-NPs) platform was capable of not only specifically binding to targeted cancer cells, effectively delivering doxorubicin (DOX), but also visualizing the targeted cancer cells. The TT-RBC-NPs achieved an extended-release profile, with the majority of the drug release occurring within 5 days. The TT-RBC-NPs enabled enhanced cytotoxic efficacy against EpCAM positive MCF-7 breast cancer over the non-targeted NPs. Additionally, fluorescence images of the targeted cancer cells incubated with the TT-RBC-NPs visually indicated the increased cellular uptake of TT-RBC-NPs inside the breast cancer cells. Taken together, this TT-RBC-NP platform sets the foundation for the next-generation stealth theranostic platforms for systemic cargo delivery for treatment and diagnostic of cancer.

Parkinson’s disease (PD), a progressive neurodegenerative disorder, presents significant challenges in long-term management due to the limitations of conventional oral dopaminergic therapy. Pramipexole dihydrochloride (Px), though clinically effective, is associated with gastrointestinal side effects and reduced compliance, especially in patients with dysphagia. To address these challenges, we developed a transdermal drug delivery system that integrates Px-loaded chitosan nanoparticles within dissolvable microneedle arrays. This hybrid platform combines the sustained release capability of polymeric nanoparticles with the minimally invasive administration of microneedles. The system is designed to penetrate the stratum corneum, dissolve upon insertion, and release Px nanoparticles for sustained dermal absorption. The microneedle arrays exhibit structural uniformity, mechanical robustness, and efficient skin insertion. The nanoparticles, in turn, enable controlled drug release while maintaining biocompatibility. Biological assessments confirmed the safety of the formulation, showing compatibility with human dermal cells and red blood cells. Moreover, ex vivo permeation studies demonstrated enhanced delivery of Px through human skin compared to free drug formulations. This work offers a promising solution for sustained, noninvasive delivery of dopaminergic therapy, with potential to improve clinical outcomes and quality of life in PD.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) is still posing a global challenge in healthcare settings. This bacterial strain is a cause of severe periprosthetic infection, thereby impairing the success of implant insertion. To address this issue, implant surface modification is required. Herein, we developed a novel multilayered silver nanoparticle/polyacrylic acid-coated Ti plate (AgNPs/PAA/Ti) using an in-house dip coater. AgNPs were synthesized and characterized. The dip-coating process was optimized based on the dipping rate, evaporation time, and coating cycle number. Uniform and reproducible coatings were achieved on Ti surfaces, with consistency verified through SEM analysis. The average size of the AgNPs was approximately 36.50 ± 0.80 nm with a PDI of 0.443 ± 0.025, and the zeta potential was measured at around –23.3 ± 2.0 mV. The maximum coating thickness of 83.5 ± 1.3 µm was observed at 15 cycles of dip coating. Moreover, our developed AgNPs/PAA/Ti plate showed both antimicrobial and biofilm-resistant performance, while also exhibiting enhanced biocompatibility with cultured MG63 osteosarcoma cells, maintaining cell viability greater than 70%. We envisage that this material holds significant promise as a candidate for medical implant devices, offering protection against MRSA-associated infection at insertion sites with low vascularity in the future.