Ultrasmall silica nanoparticles, as one type of nanocarriers featured by excellent biocompatibility and efficient renal clearance, are of rapidly growing interest for biomedical applications, particularly in oncology. Undesirably, the intrinsic issues of low site-targeting capability, short circulation time, and limited functionalities of ultrasmall silica nanoparticles severely impede their widespread application in the biomedical domain. Recent researches on surface modification for improved physical properties, enhanced site-specific abilities and multimodality imaging have been continuously emerging, which provide the prerequisite for possible application in the integration of diagnosis and treatment. On this basis, this review summarizes the most widely used synthesis approaches for well-ordered ultrasmall silica nanoparticles with uniform diameter and tunable pore size, and simultaneously highlights the diverse surface functionalization for versatile purposes and biomedical applications, including site-targeted delivery of drugs, stimuli-responsive cargo release, real-time bioimaging as well as cancer theranostics. Finally, the challenges of ultrasmall silica nanoparticles in oncology are further discussed with the aim of promoting their future clinical application.

Polymer-induced self-assembly of inorganic nanoparticles has emerged as a powerful strategy for fabrication of stimuli-responsive drug delivery nanosystems. Herein, we designed and synthesized a series of lipoic acid-capped polysarcosine-b-polycaprolactone (PSar-b-PCL) block copolymers. The self-assembly of gold nanoparticles drove by these block copolymers was systematically investigated, and the preparation of near-infrared (NIR) light-responsive PSar-decorated gold nanovesicle (PSGV) was optimized. DOX as anticancer drug was efficiently encapsulated within the cavity of PSGV. The PSGV greatly prevented doxorubicin (DOX) from premature leakage. While upon 808 nm laser irradiation, most of loaded DOX was rapidly released, along with the recovery of DOX fluorescence. Impressively, the DOX-loaded PSGV (DOX-PSGV) exhibited much higher cell uptake efficiency when compared to DOX-loaded polyethylene glycol (PEG)-coated gold nanovesicle (DOX-PEGV). Thanks to the synergistic photothermal/chemo therapy, the DOX-PSGV had highly superior antitumor efficacy in established 4T1 tumor model.