Self-Assembled Nucleotide/Saccharide-Tethering Polycation-Based Nanoparticle for Targeted Tumor Therapy

Abstract

Development of novel concepts to construct drug vehicles for efficient encapsulation of hydrophobic drugs and targeted therapy is highly desirable to biomedical science. It remains a challenge to create effective noncovalent linkage between the components within the drug vectors. In this work, we report a supramolecular approach to construct multifunctional nanoparticles, which combined tumor-targeting capability via saccharide, cell penetration via positive-charged surface, and chemotherapeutic function via drug delivery for cancer therapy. A endogenous self-associating nucleotide (guanosine monophosphate) noncovalently bonded with a hydrophobic nucleoside analogue drug (clofarabine) to form nanofibrils, which were transformed to spherical nanoparticles by assembling with a fructose/ethanolamine-functionalized starlike poly­(glycidyl methacrylate)-based cationic polymer. Noncovalent cavities within the nanoparticles were created, through the nucleotide self-association, and acted as linkage between the hydrophilic cationic polymer and the drug. The saccharide-tethering polycation and nucleotide components were labeled with fluorescent dyes, respectively, to image the endocytosis and biodistribution. In vitro and in vivo results show that the functional nanoparticles exhibited good capabilities of the targeted accumulation of the nanoparticles and delivery of drugs in cancer cells and tumor sites, leading to a robust anticancer effect.

Mannose-functionalized star polycation mediated CRISPR/Cas9 delivery for lung cancer therapy

“…3-(Benzylsulfanylthiocarbonylsulfanyl)-pentaerythritol (BSPER) preparation was performed by following the previously reported method. 32 The area ratios of peaks at δ = 7.35, 4.65, 4.12, 3.57 and 2.79 ppm were 5 : 2:2 : 2:2 in the 1 H NMR spectra of BSPER. This confirmed that BSPER was successfully synthesized (Fig.…”

Reversing Anticancer Drug Resistance by Synergistic Combination of Chemotherapeutics and Membranolytic Antitumor β-Peptide Polymer

“…For systemic administration, two different types of anticancer agents may have significantly different pharmacokinetic and tissue distribution characteristics, , so it is difficult to keep their optimal synergistic ratio at the tumor site. To address this obstacle, we developed a codelivery system of MM 60 CO 40 and DOX using hyaluronic acid-poly­( N -isopropylacrylamide) (HA-PNIPAM) nanogel and the mean time to prolong the blood circulation time. − The HA-PNIPAM polymer was synthesized to have a PNIPAM grafting rate at about 33%, and the structure was confirmed by 1 H NMR (Figure S5). When the temperature reached above the lower critical solution temperature (LCST) of PNIPAM, PNIPAM shrank into a hydrophobic core, and HA formed a hydrophilic shell to obtain the nanogels that could be loaded with DOX in the hydrophobic core and bound with the positively charged MM 60 CO 40 at the hydrophilic HA shell via electrostatic interaction (Figure ).…”

A multifunctional theranostics nanosystem featuring self-assembly of alcohol-abuse drug and photosensitizers for synergistic cancer therapy

“…For these nDDSs, the efficacy and safety of the nanosystem is always a vital concern for their biomedical application. [21][22][23] Polyamidation (PAMAM) dendrimers have a wide range of medical applications resulting from their branched-molecule structure. [24][25][26][27] The ability of nDDSs for highly selective codelivery of PSs and chemotherapy molecules is due to the structure of PAMAM dendrimers, which can bring a suitable space and facilitate encapsulation.…”