Advancements in nanoparticle-based treatment approaches for skin cancer therapy

Abstract

Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.

Keywords: Melanoma; Metal nanoparticles; Nanomaterials; Nanotechnology; Polymer; Skin carcinoma.

Fig. 1

Diagrammatic representation of basal cell carcinoma, squamous cell carcinoma, and melanoma

Fig. 2

An illustration of melanoma progression

Fig. 3

Diagrammatic representation of current treatment approaches for skin cancer and their limitations

Fig. 4

Schematic representation of utilization of nanoparticles in skin cancer therapy

Fig. 5

A Diagrammatic representation of dacarbazine (DTIC) imbibed cancer cell membrane camouflaged mesoporous silica nanoparticle synthesis process (DTIC@CMSN). B Schematic illustration of antitumor immune response induced by DTIC@CMSN merged with anti-programmed cell death protein 1 antibody (aPD1), reproduced with permission from [107], licensed under CC BY 4.0

Fig. 6

In vivo construction of immune cell-based nanomedicine carriers and initial PTT treatment enhance hitchhiking delivery into the tumor and improve antitumor immunotherapy. A E. coli OMVs are coated on both CD-GNPs and ADA-GNPs to prepare bacteria-mimetic nanoparticles. B Selective phagocytosis of bacteria-mimetic nanoparticles by phagocytic immune cells induces OMV degradation and subsequent intracellular aggregation of GNPs mediated by CD-ADA host–guest interactions, leading to photothermal property due to the plasmonic effects of GNP aggregates. The large size of intracellular GNP aggregates also inhibits the leakage during in vivo cell-hitchhiking delivery. Because of the inflammatory tropism to melanoma, immune cells achieve the targeted delivery of intracellular GNP aggregates to the tumor tissues. C Initial PTT treatment of GNP aggregates induces tumor damage that subsequently enhances inflammatory signals and provides positive feedback to recruit more immune cells (including the carriers) for enhanced antitumor therapy. Secondary photothermal treatment (PTT) of Mixture induces tumor cell immunogenic cell death (ICD) and activates antitumor immune response, further strengthened by immune checkpoint blockage (aPD-L1), reproduced with permission from [168], licensed under CC BY 4.0

Fig. 7

Schematic illustration of the design and therapeutic strategy of SHP. Part I: Synthesis of PAE and preparation of SHP micelle from the PAE, HA and SCP. Part II: Topical application of SHP/SiRNA induces survivin slicing in skin melanoma. (1) SHP/SiRNA nanocomplexes penetrate through the skin stratum corneum and target to melanoma locates at the interface of epidermis and dermis. (2) SHP/SiRNA-survivin nanocomplexes are uptaken by melanoma cells. (3) SHP/SiRNAsurvivin nanocomplexes escaped from the lysosome, release the siRNA that bind to the targeting RNA, followed by slicing survivin, which possesses the great potential to induce the significant apoptosis to melanoma cells in vitro and retard the melanoma progression in vivo, reproduced with permission from [249], copyright 2020, Elsevier

Fig. 8

Illustration of cRGD-installed reduction-responsive crosslinked nanotherapeutics from star PLGA-lipoic acid conjugate (cRGD-sPLGA XNPs) for enhanced DOX delivery to B16F10 melanoma bearing mice in vivo, reproduced with permission from [277], copyright 2019, American Chemical Society

Fig. 9

Schematic illustration of the formation of P/LNV loaded with tumor vaccines and IDO inhibitor (P/LNV@IDO/AE/CpG) and the action mechanism for immunotherapy (A) Preparation of P/LNV@IDO/AE/CpG. B Combination immunotherapy induced by P/LNV@IDO/AE/CpG. Naive dendritic cells (DCs) are activated and their maturation is induced by the antigens delivered by P/LNV@IDO/AE/CpG, which then present the processed peptide antigens to T cells, causing a strong cytotoxic T-lymphocyte (CTL) response. Tumor cells would be attacked by effector T cells. Besides, the presentation of 1-MT would inhibit the activity of IDO by decreasing the oxidization of tryptophan (Trp) to kynurenine (Krn), which further enhanced the antitumor immune response. Together, P/LNV@IDO/AE/CpG resulted in a superior combination immunotherapy against melanoma, reproduced with permission from [334], copyright 2021, Royal Society of Chemistry

Fig. 10

Diagrammatic representation of spatiotemporally controlled pulsatile release microneedle drug delivery system for the treatment of melanoma, reproduced with permission from [377], licensed under CC BY 4.0