Self-assembled polymeric nanocarrier-mediated co-delivery of metformin and doxorubicin for melanoma therapy

Abstract

Malignant melanoma is a life-threatening form of skin cancer with a low response rate to single-agent chemotherapy. Although combined therapies of metformin (MET) and doxorubicin (DOX) are effective in treating a variety of cancers, including breast cancer, their different physicochemical properties and administration routines reduce the effective co-accumulation of both drugs in tumors. Nanoparticles (NPs) have been demonstrated to potentially improve drug delivery efficiency in cancer therapy of, for example, liver and lung cancers. Hence, in this study, we prepared pH-sensitive, biocompatible, tumor-targeting NPs based on the conjugation of biomaterials, including sodium alginate, cholesterol, and folic acid (FCA). As expected, since cholesterol and folic acid are two essentials, but insufficient, substrates for melanoma growth, we observed that the FCA NPs specifically and highly effectively accumulated in xenograft melanoma tumors. Taking advantage of the FCA NP system, we successfully co-delivered a combination of MET and DOX into melanoma tumors to trigger pyroptosis, apoptosis, and necroptosis (PANoptosis) of the melanoma cells, thus blocking melanoma progression. Combined, the establishment of such an FCA NP system provides a promising vector for effective drug delivery into melanoma and increases the possibility and efficiency of drug combinations for cancer treatment.

Targeted Delivery of Drugs and Genes Using Polymer Nanocarriers for Cancer Therapy

“…At present, there are many options for achieving tumor-targeted gene delivery. For example, our previous work mainly focused on passive targeting through the enhanced permeability and retention (EPR) effect or through cancer cellspecific ligands (such as antibodies, peptides, and surface mountants) [111,112]. Active targeting enhances the targeting ability of NPs to maximize tumor distribution and deep tissue penetration.…”

“…Polymer NPs play a central role in a variety of applications, such as drug delivery, medical imaging, and the early detection of disease [126][127][128]. Polymer NPs are particles obtained from natural (chitosan [129], sodium alginate [111] and cyclodextrin [130], etc. ), semi-synthetic or synthetic polymers (poly(lactic-co-glycolic acid)poly(ethylene glycol) (PLGA-PEG) [131], N-(2-hydroxypropyl)methacrylamide (HPMA) [132] and poly(acrylamide) (PAM) [133]).…”

“…In addition, an important advantage of polymer nanocarriers is that drugs with different physical and chemical properties can be co-encapsulated in the same nanocarrier and delivered to tumor cells simultaneously to achieve combined therapy [218]. In our previous research, we reported the self-assembled polymer nanocarrier-mediated co-delivery of metformin and Dox for the treatment of melanoma [111]. We mainly used folic acid-sodium alginatecholesteric amphoteric polymer NPs to co-deliver metformin and Dox to melanoma tissues, and to inhibit tumor progression by inducing PANoptosis (pyroptosis, apoptosis, and necroptosis) of melanoma cells (Figure 2).…”

“…Figure 2.The self-assembled polymeric nanocarrier-mediated co-delivery of metformin and doxorubicin for melanoma therapy Reproduced from Song et al[111].…”

Targeting Antibacterial Effect and Promoting of Skin Wound Healing After Infected with Methicillin-Resistant Staphylococcus aureus for the Novel Polyvinyl Alcohol Nanoparticles

“…Recent reports have identified nanomedicine as an ideal approach to improve the efficiency and wound treatment. 3 Nanoparticles are ultrafine particles between 1–1000 nm in diameter, 8 that have many advantageous properties related to trauma therapy, including being biodegradable, exhibiting controlled drug release, enough drug delivery efficacy, 10 have healing properties, penetrated blood-brain barrier 11 and their ability to be used as an extracellular matrix material. 3 Many studies have shown that nanoparticles can improve antibacterial and wound-healing activities.…”