A Strategy of Limited‐Space Controlled Aggregation for Generic Enhancement of Drug Loading Capability

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Abstract
A prevalent problem of magnetic resonance imaging (MRI) contrast agents (CAs) for drug loading applications is easy aggregation. The major concern of hollow mesoporous organosilica nanoparticles (HMONs) is hard control of untimely drug leakage. To overcome both problems, a new strategy of limited‐space controlled aggregation for generic enhancement of drug loading capability is proposed. Typically, MRI CAs of exceedingly small gadolinium oxide nanoparticle (GO) and Gd poly(acrylic acid) macrochelate (GP) are exploited to load doxorubicin (D) in HMONs hollow core. The GO@D@HMONs and GP@D@HMONs without precipitation formation display much higher drug loading contents (33.0 ± 4.9%, 39.6 ± 4.0%) than GO@D and GP@D with serious precipitation generation (4.7 ± 0.5% and 14.7 ± 3.4%), which can be ascribed to the generation of GO@D and GP@D aggregates with larger sizes in HMONs hollow core than the pore size of HMONs preventing the drug leakage. The tumor microenvironment (TME)‐specific glutathione (GSH)‐triggered degradation of HMONs and the controlled drug release behaviors reinforce the chemotherapeutic efficacy and alleviate side effects on normal cells/tissues. The GSH‐activatable T1‐MRI is favorable to high contrast tumor imaging. Overall, the strategy of limited‐space controlled aggregation is promising for generic enhancement of drug loading capability of MRI CAs, realizing MRI‐guided high‐performance cancer treatments.
Funding Information
  • National Natural Science Foundation of China (32271374)

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