The formulation of aptamer-coated paclitaxel-polylactide nanoconjugates and their targeting to cancer cells.
Paclitaxel-polylactide (Ptxl-PLA) conjugate nanoparticles, termed as nanoconjugates (NCs), were prepared through Ptxl/(BDI)ZnN(TMS)(2) (BDI = 2-((2,6-diisopropylphenyl)-amido)-4-((2,6-diisopropylphenyl)-imino)-2-pentene)-mediated controlled polymerization of lactide (LA) followed by nanoprecipitation. Nanoprecipitation of Ptxl-PLA resulted in sub-100 nm NCs with monomodal particle distributions and low polydispersities. The sizes of Ptxl-PLA NCs could be precisely controlled by using appropriate water-miscible solvents and by controlling the concentration of Ptxl-PLA during nanoprecipitation. Co-precipitation of a mixture of PLA-PEG-PLA (PLA = 14 kDa; PEG = 5 kDa) and Ptxl-PLA in PBS resulted in NCs that could stay non-aggregated in PBS for an extended period of time. To develop solid formulations of NCs, we evaluated a series of lyoprotectants, aiming to identify candidates that could effectively reduce or eliminate NC aggregation during lyophilization. Albumin was found to be an excellent lyoprotectant for the preparation of NCs in solid form, allowing lyophilized NCs to be readily dispersed in PBS without noticeable aggregates. Aptamer-NCs bioconjugates were prepared and found to be able to effectively target prostate-specific membrane antigen in a cell-specific manner.
Tong
Rong
R
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Yala
Linda
L
Fan
Timothy M
TM
Cheng
Jianjun
J
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D001672:Biocompatible Materials; D004337:Drug Carriers; D011091:Polyesters; C033616:poly(lactide); D017239:Paclitaxel