A nanoparticles based theranotic drug delivery system developed by researchers, Prof. Min Zhou and his collaborators, at Zhejiang University (ZJU), has already shown promise in multimodal imaging-guided precision cancer therapy. The work was published on top journal “Advanced Functional Materials”, and highlighted as back cover of the journal by editorial office.

One of the major obstacles for clinical translation of functional nanoparticles is their prolonged retention in the body after systemic administration. Renal-clearable NPs which can be excreted via renal clearance system, has made it possible to overcome the toxicity by nonspecific accumulation in healthy tissues. However, the tumor uptakes of most of the renal-clearable NPs are low due to their short blood circulation time. Therefore, it is challenging to develop a nanosystem to have both high tumor accumulation property and efficient body clearable characteristics. Another challenge is to integrate multiple functions in a single-compartment nanoscale device with intrinsic physicochemical properties suitable for cancer diagnosis and therapy.

In collaboration with Prof. Mei Tian and Prof. Hong Zhang at The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhou and his associates resolved these important problems and report a novel multi-functional, biodegradable, and renal clearable theranostic agent, ultrasmall CuSNDs sealed DOX-mesoporous silica NPs (MDNs) that can be used for PET, photoacoustic, and thermal imaging, be inhibited tumor growth by the NIR laser mediated controlled DOX release, and be efficiently cleared from the body via the renal-urinary system.

In this study, DOX was firstly loaded into the pores of the biodegradable mesoporous silica NPs (MSN), which could be later used for the cancer chemotherapy. Then, ultrasmall sized CuSNDs were adsorbed onto the surface of MSNs allowing their application of laser-triggered PTT and drug release simultaneously. As the size of the CuSNDs perfectly matches the pores of the MSNs, thus most of the MSNs’ pores were sealed by the coated CuSNDs to prevent the DOX premature release simultaneously. After laser irradiation, the constructure of the MDN were cracked at high temperature, and the DOX can be triggered release from the nanosystem. Because CuSNDs sealed the pore of the DOX-ladened the porous silical nanoparticles, the premature drug release can be prevented. But the DOX can be triggered release by the NIR laser induced the fracture of silica constructure. The biodegradable, renal-clearable, single-compartment nanoscale device integrating PET, photoacoustic, and thermal triple-modal imaging, and chemo-photothermal combination therapy, has not previously been collectively achieved. Nanoscale device such as this may overcome one of the major concerns associated with the clinical translation of functional nanoparticles, which is toxic effect due to nonspecific accumulation of NPs in healthy organs.   

Such biodegradable and clearable single-compartment theranostic agents produced by a highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials to clinical practice.