Single‐Molecule All‐In‐One (SMALL) Dendritic Dots for Precise Cancer Theranostics

Multifunctional nanoparticles with diverse cargos have been extensively developed for efficient cancer theranostics. However, the requirement of additional components would result in stochastic functionalization, interfering with the precise structure and desired characteristics. Thus, it is requisite and challenging to develop multifunctional nanoparticles with a single component. Herein, we report a universal, modular and scalable design approach for constructing a type of single-molecule all-in-one (SMALL) dendritic dots (DDs) with well-defined functional architectures for customizable theranostics. These SMALL DDs are prepared through dendrimer-based divergent synthesis by orthogonal protection, selective deprotection, and precise conjugation. To demonstrate the feasibility of the strategy, we synthesized a type of perylenediimide (PDI)-cored and camptothecin-loaded polylysine dendrimer-based SMALL DDs. These DDs possess precise structure, tunable drug loading, well-defined particle size, and bright and stable fluorescence. The SMALL DDs exhibit long blood circulation, superior tumor accumulation, and tumor-associated enzyme-responsive drug release and generate potent antitumor activity in mice bearing hepatocellular carcinoma. The SMALL DDs integrate imaging probes, drug molecules, and targeting and responsive ligands into a single molecule, which provides a strategy to solve the dilemma of multifunctionality and structural precision and is promising for cancer theranostics.