Hematoporphyrin encapsulated PLGA microbubble for contrast enhanced ultrasound imaging and sonodynamic therapy

Abstract

The purpose of this study was to develop a sonosensitizer-loaded multi-functional ultrasound (US) contrast agent for both tumour therapy and imaging. The hematoporphyrin (HP)-encapsulated poly(lactic-co-glycolic acid) microbubbles (HP-PLGA-MBs) were prepared and filled with perfluorocarbon gases. The enhancement of US imaging and its sonodynamically induced anti-tumour effect were evaluated by both in vitro and in vivo experiments. The HP-PLGA-MBs have a narrow size distribution and smooth surface with a mean diameter of 702.6 ± 56.8 nm and HP encapsulation efficiency of 63.50 ± 1.26% and drug-loading efficiency of 2.15 ± 0.13%. The HP-PLGA-MBs could well enhance the ultrasound imaging both in vitro and in vivo. A significant anti-tumour effect was obtained by HP-PLGA-MBs mediated sonodynamic therapy. The tumour growth rate and the tumour proliferation index were the lowest in the HP-PLGA-MBs plus sonication group. And the tumour cell apoptotic index was the biggest in the HP-PLGA-MBs plus sonication group. In conclusion, a sonosensitizer-loaded multi-functional contrast agent was constructed and the feasibility was demonstrated, which might provide a novel strategy for tumour imaging and therapy.

A versatile, stimulus-responsive nanoparticle-based platform for use in both sonodynamic and photodynamic cancer therapy

“…We are unaware of any study describing the preparation of HP-loaded PLGA nanoparticles, although a previous study has described encapsulation of HP in PLGA microbubbles (approximate dia. 2 µm) and in that study the encapsulation efficiency was 64% [20] which approximates the 70% encapsulation efficiency reported here. The high levels of association between HP and PLGA in both studies may result from the limited solubility of HP in aqueous media which limits is use in either PDT or SDT.…”

Sonodynamic Therapy: Advances and Challenges in Clinical Translation

“…Future challenges to improve this technique involve notably obtaining a deeper knowledge and efficient methods to handle cavitation. First, additional Accuracy is slightly reduced when using dual-frequencies; US power is not the only relevant parameter: exposure configuration and timing are important Treatment monitoring US contrast agents loaded with sensitizers and gas for cavitation imaging 84 ; SDT process monitoring by positron emission tomography 86 ; Association of sensitizers with manganese ions for high magnetic resonance imaging performance 87 Most of studies did not report proper cavitation monitoring mechanistic studies have to be conducted on the sonodynamic effect. A better understanding of the interaction of sonosensitizers with cavitation will help adapt cavitation generation to optimize the resulting effects while limiting unnecessary energy deposition of undesired mechanical effects.…”

“…For this concern, contrast agents carrying HP and filled with perfluorocarbon gasses were developed. 84 These contrast agents of 700 nm enabled the enhancement of tumor imaging in vivo as well as an increase in the antitumor effect. This process would constitute monitoring at step B: creating cavitation at the correct location.…”

A Review of Low-Intensity Ultrasound for Cancer Therapy

“…The combining of the sonosensitizer with a microbubble contrast agent may lead to important future developments in sonodynamic therapy (Zheng et al 2012). The combined agent can then be classified as a theranostic agent as the entry of the loaded microbubbles into the tumor vasculature can be monitored by ultrasound imaging and, once detected within the tumor by diagnostic ultrasound, sonodynamic therapy can be initiated.…”