Dual-Drug Conjugated Glyco-Nanoassemblies for Tumor-Triggered Targeting and Synergistic Cancer Therapy

Katmerlikaya T. G., DAĞ A., Ozgen P. S., Ersen B. C.

ACS APPLIED BIO MATERIALS, cilt.5, sa.11, ss.5356-5364, 2022 (ESCI) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 5 Sayı: 11
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1021/acsabm.2c00749
  • Dergi Adı: ACS APPLIED BIO MATERIALS
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, BIOSIS, Compendex, MEDLINE
  • Sayfa Sayıları: ss.5356-5364
  • Anahtar Kelimeler: glyco-nanoassemblies, gemcitabine, cisPt, cellular uptake, synergistic chemotherapy, GEMCITABINE, DELIVERY
  • Marmara Üniversitesi Adresli: Hayır

Özet

Drug-conjugated nanoassemblies potentiate the efficiency of anticancer drugs through the advantages of high drug-loading capacity and passive/active targeting ability in cancer therapy. This study describes the synthesis of gemcitabine (Gem) and cisplatin (cisPt) dual-drug-functionalized glyco-nanoassemblies (GNs) for anticancer drug delivery systems. It also investigates the pH-triggered drug delivery of the conventional anticancer drug cisPt. A Gem-functionalized well-defined glycoblock copolymer backbone (P(iprFruMA-b-MAc)-Gem), which consists of fructose and methacrylic acid segments, was synthesized via a reversible addition-fragmentation chain transfer (RAFT) polymerization method. Following the hydrolysis of the protecting groups on the backbone copolymer, cisPt functionalization of P(FruMA-b-MAc)-Gem in aqueous media was carried out during the transformation of glycoblock polymers into self-assembled spherical glyco-nanoassemblies (GN3). Monodrug-functionalized glyco-nanoassemblies were also prepared either with Gem (GN1) or cisPt (GN2) to compare the synergetic effect of dual-drug conjugated glyco-nanoassemblies (GN3). The sizes of glyco-nanoassemblies GN1, GN2, and GN3 were found as 5.76 +/- 0.64, 59.80 +/- 0.13, and 53.80 +/- 3.90 nm and dispersity (D) values as 0.476, 0.292, and 0.311 by dynamic light scattering (DLS) measurement, respectively. The in vitro studies revealed that the drug-free glyco-nanoassemblies are biocompatible at concentrations higher than 296 mu g/mL. The drug-conjugated glyco-nanoassemblies (GN1 and GN2) exhibited in vitro cytotoxicity against human breast cancer cell lines of MDA-MB-231 comparable to free Gem and cisPt, illustrating an efficient drug release into the tumor environment. Additionally, GNs exhibited higher selectivity and preferential cellular internalization in MDA-MB-231 when compared to healthy cell lines of CCD-1079Sk. These dual-drug conjugated GNs can effectively enhance the killing of cancer cells and increase synergistic chemotherapy.