Abstract
This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.
Highlights
In recent years, rapidly developed high intensity focused ultrasound (HIFU) has been regarded to be a new technique for non-invasive ablation of local tumors, focusing low-energy ultrasound (US) on the target areas in a certain way, which treats the lesion via cell necrosis[1] caused by the instant heat effect, cavitation effect, mechanical effect, and so on
UV spectrometry showed that the Hematoporphyrin monomethyl ether (HMME)/poly(lactic-co-glycolic acid) (PLGA) microcapsules covered a wide absorption wavelength range in the UV visible region, with a strong absorption band at 418 nm and four absorption peaks between 500–700 nm (Fig. 2f)
SEM and TEM revealed the basic morphology of the HMME/PLGA microcapsules, as a large number of black HMME particles embedded in the PLGA spherical shell
Summary
Rapidly developed high intensity focused ultrasound (HIFU) has been regarded to be a new technique for non-invasive ablation of local tumors, focusing low-energy ultrasound (US) on the target areas in a certain way, which treats the lesion via cell necrosis[1] caused by the instant heat effect, cavitation effect, mechanical effect, and so on. The US propagation path, leading to severe side effects[7,8,9] For these reasons, synergistic agents have emerged to maintain the advantage of non-invasive HIFU treatment, which increase the energy deposition in the target area by affecting the acoustic environment. Poly (lactic-co-glycolic acid) (PLGA) is one of the preferential candidates for drug delivery, molecular imaging, and tissue engineering in clinic, which is featured by high stability, biocompatibility, biodegradability, and long blood circulation time in vivo. In this study, using HMME with excellent imaging and SDT properties together with PLGA as film-forming material with great biocompatibility, a multifunctional microcapsule was established.
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