Background: Multifunctional nanoplatforms with diagnostic-imaging and targeted therapeutic functionality (
theranostics) are of great interest in the field of precision nanomedicine. The emerging sonodynamic
therapy (SDT) combined with sonosensitizers under the guidance of photoacoustic (PA) imaging is highly expected to accurately eliminate
cancer cells/tissue. Methods: Unique core/shell-structured
theranostic FA-HMME-MNPs-PLGA nanoparticles (FHMP NPs, FA:
folate, HMME:
hematoporphyrin monomethyl ether, MNPs:
melanin nanoparticles, PLGA:
poly (lactic-co-glycolic) acid) were constructed by the integration of MNPs (for PA imaging) in the core and HMME in the shell for enhanced PA imaging-guided SDT, which were further functionalized with a
tumor-targeting
ligand, FA. The PA imaging-guided SDT was systematically and successfully demonstrated both in vitro and in vivo. The high biosafety of FHMP NPs was also systematically evaluated. Results: The synthesized FHMP NPs with a broad optical absorption not only possess high PA-imaging contrast enhancement capability but also exhibit significant SDT efficiency. Importantly, such a PLGA based nanoplatform improved light stability of HMME, enhancing sonodynamic performance and facilitated delivery of MNPs to the
tumor region. Meanwhile, a combined effect between HMME and MNPs was discovered and verified. Furthermore, a sonosensitizer assisted by ultrasound irradiation engenders
reactive oxygen species (ROS)-mediated cytotoxicity toward
tumor cells/tissue. Both in vitro cell-level and systematic in vivo xenograft evaluations on
tumor-bearing mice demonstrated that the selective killing effect of ROS on
tumor cells was assisted by FHMP NPs, which played an active role in the suppression of
tumor growth with high biosafety. Conclusion: A
theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against
breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique
theranostic nanoplatform with multiple capabilities paves a new way toward
personalized medicine by rational utilization.