Multifunctional polypeptide-based polymersome for chemophotothermal therapy of melanoma in vitro and in vivo

Abstract

To date, combination therapy using chemo-photothermal therapy (Ch-PTT) has attracted tremendous interest due to its efficient ablation of cancerous cells. Furthermore, there are several advantages to using peptide-based nanocarriers for theranostic nanoplatforms, such as excellent biocompatibility and biodegradability, significant encapsulation efficacy for lipophilic drugs with negligible drug leakage, excellent stability, and excellent enzymatic degradation. In the current study, a multifunctional theranostic system based on polymersome (vesicular nanocarrier of self-assembled amphiphilic polymer) was developed for targeted Ch-PTT and x-ray CT imaging of melanoma cancer. For this purpose, using ring opening polymerization (ROP) of γ-benzyl l-glutamate-N-carboxyanhydride (LG-NCA) lipophilic polypeptide PLG (poly(γ-benzyl-l-glutamate) was synthesized and covalently linked to bifunctional COOH-PEG-NH2. Next, polypeptide-based polymersome nanocarier based on amphiphilc PEG-PLG was fabricated and co-encapsulated with hydrophilic gold nanorod (AuNR) and lipophilic curcumin (CUR) in aqueous core and lipophilic bilayer of polymersome (P-AuNR-CUR), respectively. Then, Sgc8-c aptamer were decorated on the polymersome surface (Apt-P-AuNR-CUR) for targeted delivery, and the size of P-AuNR-CUR and Apt-P-AuNR-CUR were determined using DLS device (174.3 ± 5.95 and 206 ± 52, respectively). NIR (near-infrared)-laser-triggered drug delivery release performance of multifunctional polymersome was demonstrated in both citrate and phosphate buffer saline. According to both in vitro and in vivo studies, NIR-responsive polymersomes possess remarkable therapeutic efficacy for Chemo-PTT in comparison to individual cancer therapy. Furthermore, the diagnostic capability of the designed nanoplatform was confirmed using in vivo CT scan imaging 6 h post-intravenous injection.