Abstract
Photodynamic therapy (PDT) has shown great promise in breast cancer treatment. However, simplex target ligand modification or stimuli release cannot meet the requirement of effective drug delivery to solid tumor tissue. To overcome continuous bio-barriers existing in the tumor microenvironment, multi-stage response drug delivery was desirable. Herein, we developed a unique tumor microenvironment tailored nanoplatform for chlorin e6 (Ce6) delivery. We chose bovine serum albumin (BSA) as “mother ships” material for effective tumor periphery resident, cyclopamine (CYC) as extracellular matrix (ECM) inhibitor and synergistic anti-tumor agent, and diselenide containing amphiphilic hyaluronic acid-chlorin e6 polymers (HA-SeSe-Ce6) synthesized as “small bombs” for internal tissue destruction. The above three distinct function compositions were integrated into an independent CYC and HA-SeSe-Ce6 co-delivery albumin nano-system (ABN@HA-SeSe-Ce6/CYC). The obtained nano-system presents good biocompatible, long circulation and effective tumor accumulation. After entering tumor microenvironment, CYC gradually releases to disrupt the ECM barrier to open the way for further penetration of HA-SeSe-Ce6. Subsequently, targeted tumor cell internalization and intracellular redox response release of Ce6 would achieve. Moreover, CYC could also make up the deficiency of Ce6 in hypoxia area, owing to its anti-tumor effect. Improved therapeutic efficacy was verified in a breast cancer cell line and tumor-bearing mice model.
Highlights
Among various emerging therapies, photodynamic therapy (PDT) is a promising noninvasive therapeutic method for superficial tumors, such as breast cancer (Agostinis et al, 2011; Wang D. et al, 2018)
The ABN@Hyaluronic acid (HA)-sese-chlorin e6 (Ce6)/CYC delivery system is consist of three functional parts
The assembling process is driven by the bovine serum albumin (BSA) hydrophobic sites exposure and hydrophobic nucleation effects of hydrophobic agents (Ce6 and CYC)
Summary
Photodynamic therapy (PDT) is a promising noninvasive therapeutic method for superficial tumors, such as breast cancer (Agostinis et al, 2011; Wang D. et al, 2018). Programmable Ce6 Delivery via Cyclopamine of photosensitizers leads to serious side effects (Liu et al, 2017). Improved delivery of hydrophobic photosensitizers leveraging nanoscale system is desirable. The various sophisticated chemical design and multi-functional nanoscale systems have developed, cancer nanomedicine still facing challenges for enhancing clinical benefits. Just target ligand modified and stimuli release no longer meet the requirement of effective drug delivery to solid tumor tissue. Despite nanoscale substances preferentially accumulate in tumor tissue than in normal tissue due to permeability and retention effect (EPR effect), abnormal tumor microenvironment with heterogeneous structure often leads to the perivascular area and tumor periphery resident of nanoparticles (Overchuk and Zheng, 2018). The design of tumor microenvironment tailored multi-stage photosensitizers delivery is essential
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