Search

Current therapeutic approaches for skin cancer face significant challenges, including wound infection, delayed skin regeneration, and tumor recurrence. To overcome these challenges, an injectable adhesive near-infrared (NIR)-responsive hydrogel with time-dependent enhancement in viscosity is developed for combined melanoma therapy and antibacterial wound healing acceleration. The multifunctional hydrogel is prepared through the chemical crosslinking between poly(methyl vinyl ether-alt-maleic acid) and gelatin, followed by the incorporation of CuO nanosheets and allantoin. The synergistic inherent antibacterial potential of CuO nanosheets, the regenerative and smoothing effect of allantoin, the extracellular matrix-mimicking effect of gelatin, and the desirable swelling behavior of the hydrogel results in fast wound recovery after photothermal ablation of the tumor. Additionally, the hydrogel can serve as an alternative to sutures owing to its tissue adhesiveness ability, which can further render it the merits for accelerated repair of abdominal lesions while acting as a biocompatible barrier to prevent peritoneal adhesion.

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and pharmacokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is intimately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.

Intravenously administered nanocarriers suffer from off-target distribution, pre-targeting drug leakage, and rapid clearance, limiting their efficiency in tumor eradication. To bypass these challenges, an injectable hydrogel with time- and temperature-dependent viscosity enhancement behavior and self-healing property are reported to assist in the retention of the hydrogel in the tumor site after injection. The cancer cell membrane (CCM) and sorafenib are embedded into the hydrogel to elicit local tumor-specific immune responses and induce cancer cell apoptosis, respectively. In addition, hyaluronic acid (HA) coated Bi2S3 nanorods (BiH) are incorporated within the hydrogel to afford prolonged multi-cycle local photothermal therapy (PTT) due to the reduced diffusion of the nanorods to the surrounding tissues as a result of HA affinity toward cancer cells. The results show the promotion of immunostimulatory responses by both CCM and PTT through the release of inflammatory cytokines from immune cells, which allows localized and complete ablation of the breast tumor in an animal model by a single injection of the hydrogel. Moreover, the BiH renders strong antibacterial activity to the hydrogel, which is crucial for the clinical translation of injectable hydrogels as it minimizes the risk of infection in the post-cancer lesion formed by PTT-mediated cancer therapy.