Polymeric Nanoparticles with a Sera-Derived Coating for Efficient Cancer Cell Uptake and Killing

Abstract

Nanoparticle-mediated cancer drug delivery remains an inefficient process. The protein corona formed on nanoparticles (NPs) controls their biological identity and, if optimized, could enhance cancer cell uptake. In this study, a hyperbranched polyester polymer (HBPE) was synthesized from diethyl malonate and used to generate NPs that were subsequently coated with normal sera (NS) collected from mice. Cellular uptake of NStreated HBPE-NPs was compared to PEGylated HBPE-NPs and was assessed using MDA-MB-231 triple-negative breast cancer (TNBC) cells as well as endothelial and monocytic cell lines. NStreated HBPE-NPs were taken up by TNBC cells more efficiently than PEGylated HBPE-NPs, while evasion of monocyte uptake was comparable. NS coatings facilitated cancer cell uptake of HBPE-NPs, even after prior interaction of the particles with an endothelial layer. NS-treated HBPE-NPs were not inherently toxic, did not induce the migration of endothelial cells that could lead to angiogenesis, and could efficiently deliver cytotoxic doses of paclitaxel (taxol) to TNBC cells. These findings suggest that HBPE-NPs may adsorb select sera proteins that improve uptake by cancer cells, and such NPs could be used to advance the discovery of novel factors that improve the bioavailability and tissue distribution of drugloaded polymeric NPs.

Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma

“… Expression of CCT subunits in neuroblastoma cell lines are comparable to metastatic TNBC cells. (A) RNA expression for the nine CCT subunits in IMR-32 and SK-N-AS cells was acquired from next-generation RNA sequencing data ( 33 ). (B) Relative mRNA expression for total CCT2 and CCT3 was determined by RT-qPCR (n=4).…”

“…For CT20p-based treatments, hyperbranched polyester nanoparticles (NP) were utilized. NP were synthesized and encapsulated with cargo as described previously ( 33 ). NP were loaded with either 1,1’-Dioctadecyl-3,3,3’,3’-Tetramethylindocarbocyanine Perchlorate (DiI dye) (ThermoFisher) or CT20p (Acetyl – VTIFVAGVLTASLTIWKKMG – Amine) peptide (Biopeptide Inc) as previously described ( 33 , 34 ).…”

“…NP were synthesized and encapsulated with cargo as described previously ( 33 ). NP were loaded with either 1,1’-Dioctadecyl-3,3,3’,3’-Tetramethylindocarbocyanine Perchlorate (DiI dye) (ThermoFisher) or CT20p (Acetyl – VTIFVAGVLTASLTIWKKMG – Amine) peptide (Biopeptide Inc) as previously described ( 33 , 34 ). DiI-loaded NP (0.02-0.1 mg) was used to assess uptake by IMR-32 cells and to detect any non-specific toxicity associated with NP carrier.…”

Macromolecules Absorbed from Influenza Infection-Based Sera Modulate the Cellular Uptake of Polymeric Nanoparticles

“…The HBPE polymer was synthesized following our previously published protocol [ 19 ]. To generate HBPE-NPs and encapsulate them with 1,1′-Dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) dye (Life Technologies, Thermo Fisher Scientific, Waltham, MA, USA) or 1,1′-Dioctadecyl- 3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) dye (Life Technologies, Thermo Fisher Scientific, Waltham, MA, USA), 10 milligrams (mg) of HBPE polymer was mixed with 1 microgram (µg) of DiI or DiR dye and dissolved at 100 mg/milliliter (mL) in dimethyl sulfoxide (DMSO) (Thermo Fisher Scientific, Waltham, MA, USA).…”

“…Incubating NPs with normal sera enables insight into which protein components of blood may be influencing the biodistribution of NPs in vivo under native conditions, as has been shown for albumin [ 16 ] or apolipoproteins [ 17 ]. Incubating polymeric NPs, formed using a hyperbranched polyester (HBPE) polymer optimized by our lab [ 18 , 19 ], with normal mouse sera enhanced breast cancer cell uptake and improved delivery of anti-cancer drugs compared to PEGylated HBPE-NPs [ 19 ]. However, pre-treatment of HBPE-NPs with normal mouse sera did not reduce monocyte uptake (e.g., THP-1 cells).…”