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Enhanced Cytotoxicity to Cancer Cells by Codelivery and Controlled Release of Paclitaxel‐loaded Sirolimus‐conjugated Albumin Nanoparticles
Author(s) -
Behrouz Hossein,
EsfandyariManesh Mehdi,
Khoeeniha Mohammad Kazem,
Amini Mohsen,
Shiri Varnamkhasti Behrang,
Atyabi Fatemeh,
Dinarvand Rassoul
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12750
Subject(s) - paclitaxel , chemistry , sirolimus , viability assay , pi3k/akt/mtor pathway , cytotoxicity , conjugated system , pharmacology , cell , cancer , biochemistry , medicine , in vitro , signal transduction , organic chemistry , polymer
Recently, it is suggested that mTOR signaling pathway is an important mediator in many cancers especially breast cancer. Therefore, effects of sirolimus as a mTOR inhibitor in breast cancer have been studied in combination with paclitaxel with or without controlled release effect. In this work, we prepared a water‐soluble formulation of sirolimus‐conjugated albumin nanoparticles loaded with paclitaxel, to study the effects of sirolimus concentration when it releases more later than paclitaxel in comparison with sirolimus–paclitaxel‐loaded albumin nanoparticles. Also effects of paclitaxel loading on cytotoxic properties of nanoparticles were studied. Sirolimus was succinylated at 42‐ OH with enzymatic reaction of Candida antarctica lipase B, and then its carboxylic group was activated with EDC / NHS and conjugated to the lysine residues of albumin. Paclitaxel was loaded on albumin surface by nab technique in concentration range of 0–10 μ g/mL. Sirolimus‐conjugated nanoparticles with 0.01 μ g/mL paclitaxel showed lowest cell viability of 44% while it was 53% for non‐conjugated nanoparticles in MDA ‐ MB ‐468 cell lines after 48 h (p‐value = 0.003). In MCF ‐7 cell lines, sirolimus‐conjugated nanoparticles with 0.1 μ g/mL paclitaxel showed lowest cell viability of 35.69% while it was 48% for non‐conjugated nanoparticles after 48 h (p‐value = 0.03). We guess that when cancer cell lines arrest in G2‐M by anticancer drugs like paclitaxel, Akt activates mTOR to make cells continue living, then inhibiting mTOR can enhance anticancer effects.