Cancer cells are co-evolved with diverse stromal cells to promote their progression and metastasis. The diverse stroma cells and multiple extracellular matrix (ECM) components form an abominable barrier of tumor stroma, which severely hampers intratumoral drug penetration and accessibility to cancer cells. Although nanosized formulations can reach the tumor sites with high accumulation, they are usually ineffective to circumvent the tumor stroma barriers and access the cancer cells in tumor, significantly compromising their antitumor effects.

To address this issue, scientists from the Shanghai Institute of Materia Medica (SIMM) of the Chinese Academy of Sciences (CAS) propose abioinspired lipoproteins (bLP)-mediated strategy, aiming at inducing photothermia to disrupt the TSM barriers and augmenting the accessibility of second-wave nanoparticles to cancer cells to suppress tumor relapse and metastasis. This research was published online in Nature Communications.

In this work, Prof. ZHANG Zhiwen and Prof. LI Yaping jointly designed a bLP system that, respectively, loaded photothermal agent of DiR (termed as D-bLP) and anticancer drug of mertansine (termed as M-bLP) for antitumor therapy.

After intravenous injection, D-bLP can reach the tumor sites with deep tumor penetration, but they are dominantly internalized by diverse stromal cells and are inaccessible to the cancer cell fractions in tumor.

Upon laser irradiation, D-bLP mediated photothermia remarkably damages the stromal cells and ECM components of the tumor stroma barriers, thereby leading to a 4.27-fold enhancement of second M-bLP accumulation in tumor, extensive permeation in whole tumor mass and 27.0-fold increase of cancer cells accessibility.

Of note, this bLP-mediated strategy produces a 95.9% inhibition on tumor growth and 97.4% suppression of lung metastasis in murine 4T1-tumor model. Moreover, the tumor relapse is completely prevented in 4/5 mice in MCF-7 tumor model.

These results validate the prominent therapeutic efficacy of bLP-mediated strategy on tumor relapse and metastasis, which was more efficient than the counterpart liposomal formulations. These findings provide deeper insights into overcoming TSM barriers to enhance nanoparticle accessibility to cancer cells for antitumor therapy.

This study is supported by National Basic Research Program of China, Strategic Priority Research Program of CAS, National Natural Science Foundation of China, Youth Innovation Promotion Association of CAS and Fudan-SIMM Joint Research Fund.

The article Linker: https://www.nature.com/articles/s41467-019-11235-4

Schematic illustration of bLP-mediated tumor stroma remodeling to enhance second nanoparticles accessibility to cancer cells (Image by ZHANG Zhiwen)

Contact:

Prof. ZHANG Zhiwen (zwzhang0125@simm.ac.cn)

(Credit: ZHANG Zhiwen; Editor: PAN Peihua)