Transforming how plastics are made, unmade, and remade through innovative research and diverse partnerships that together foster environmental stewardship is critically important to a sustainable future. Designing, preparing, and implementing polymers derived from renewable resources for a wide range of advanced applications that promote future economic development, energy efficiency, and environmental sustainability are all central to these efforts. In this Chemical Reviews contribution, we take a comprehensive, integrated approach to summarize important and impactful contributions to this broad research arena. The Review highlights signature accomplishments across a broad research portfolio and is organized into four wide-ranging research themes that address the topic in a comprehensive manner: Feedstocks, Polymerization Processes and Techniques, Intended Use, and End of Use. We emphasize those successes that benefitted from collaborative engagements across disciplinary lines.

Herein, we report the transformation of bmonomethyl itaconate, an inexpensive and biorenewable alternative to petroleum feedstocks, to the high-value monomer amethylene-c,c-dimethyl-c-butyrolactone (Me 2 MBL) through a selective addition strategy. This strategy is also applied to the synthesis of a-methylene-c-butyrolactone (MBL, tulipalin A), a monomer that can be polymerized to give materials with desirable properties (high decomposition temperature, glass transition temperature, and refractive index). Subsequent polymerization of both Me 2 MBL and MBL through reversible addition-fragmentation chain-transfer polymerization generates well-defined poly(Me 2 MBL) and poly(MBL) (PMBL). Physical characterization of poly(Me 2 MBL) shows good physical properties comparable with known PMBL materials.

The purpose of this study was to learn if a convenient 1H NMR method could be developed to serve as a tool for estimating the propensity of a given lactone to participate in ring-opening transesterification polymerization (ROTEP). The methanolysis of each of 18 lactones was initially examined in CD3OD solution in the presence of sulfuric acid as a Brønsted catalyst at ambient temperature. Once equilibrium was established, the ratio of remaining lactone to the ring-opened methyl ester/alcohol could be readily measured by NMR spectroscopy. The observed thermodynamic driving force observed for the methanol ring openings is roughly in line with the extent of ROTEP for the various classes of lactones. This is the case even though the reaction conditions for these methanolyses versus ROTEP reactions are substantially different. Qualitative evaluations of the rates of the ring-opening methanolyses were also performed, and several non-obvious relative reactivities were observed. Finally, employing this simple NMR methanolysis using low concentrations of methanol in CDCl3 is recommended as the preferred protocol for the initial evaluation of the polymerizability of any new lactone monomer that researchers may prepare in the future.

Cancer stem cells (CSCs) are considered to be key contributors to drug resistance and tumor recurrence in many solid tumors. Therapeutic approaches that specifically target these cells are needed to improve treatment outcomes in these tumor types. We are investigating CD133, a widely used surface marker to identify CSCs in colon, brain, and breast tumors. Here, we report the use of polymeric nanoparticles targeting CD133 by conjugating an anti-CD133 scFv-Fc to poly(L-lactide)-PEG-maleimide nanoparticles (anti-CD133 NPs) for effective CSC targeting. The Fc tagged anti-CD133 scFv was prepared and purified using an Expi293 expression system. Nanoparticles were prepared using flash nanoprecipitation and loaded with a hydrophobic, hydrolytically labile, silicate prodrug of paclitaxel. Flash nanoprecipitation allowed for generation of particles with a size of 232 ± 17 nm (increased to 289 ± 23 nm upon scFv conjugation), a zeta potential of -11.5 mV and a drug loading of 57 ± 8 wt% measured by HPLC. The anti-CD133 scFv-Fc was thiolated using 2-iminothiolane (2-IT) and conjugated to nanoparticles using thiol-maleimide chemistry. Thiolation of the antibody was optimized using different molar excesses of 2-IT. A binding assay using Caco-2 cells (which overexpress CD133) confirmed that thiolation of the antibody did not affect its binding, even at the highest molar excess of 2-IT used. With 200x molar excess of 2-IT, 2.9 thiols per antibody were added. Antibody conjugation was confirmed using gel electrophoresis; bands corresponding to the heavy and light chains of antibody were observed for anti-CD133 NPs after reduction but were not seen for non-reduced anti-CD133 NPs or for unconjugated particles. Cytotoxicity studies in MDA-MB-231-LM2 cells revealed maximum kill in drug loaded anti-CD133 NPs, which was significantly higher than for either non-targeted, drug-loaded nanoparticles or blank nanoparticles (p<0.05). Overall, these studies indicate the potential for using anti-CD133 scFv-Fc in conjunction with FNP-produced silicate prodrug nanoparticles of paclitaxel for efficient targeting of CSCs. Citation Format: Shubhmita Bhatnagar, Mengyuan Jin, Thomas Hoye, Jayanth Panyam. CD133-targeting silicate prodrug nanoparticles for effective cancer stem cell targeting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2880.