摘要
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM) and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D) was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
基金
financially supported by the National Basic Research Program of China(2015CB932103)
the National Natural Science Foundation of China(31771092,81521005,81690265)
the Youth Innovation Promotion Association of Chinese Academy of Sciences and Fudan-SIMM Joint Research Fund(FU-SIMM20182005,China).
作者简介
Tao Tan,These authors made equal contributions to this work;Yuqi Wang,These authors made equal contributions to this work;Corresponding authors:Yaping Li,Tel./fax:+862120231979.E-mail addresses:ypli@simm.ac.cn;Corresponding authors:Zhiwen Zhang,E-mail addresses:zwzhang0125@simm.ac.cn;Corresponding authors:Siling Wang,E-mail addresses:silingwang@syphu.edu.cn
