Organic Nanoparticle–Carbon Dots Conjugate for Multimodal Cancer Therapy

Nanoconjugates emerge as innovative theranostic probes, seamlessly combining diagnostic precision with the targeted therapeutic potential to revolutionize cancer treatment strategies. The present article delineates the design and fabrication of NIONP-CaCD conjugate between naphthalimide based organic nanoparticles (NIONPs) and Ca²⁺-doped carbon dots (CaCDs). Naphthalimide based lysosome targeting unit appended boronic acid tethered amphiphile was synthesized that formed NIONP organic nanoparticles via J-aggregation in DMSO–water. CaCDs were synthesized via hydrothermal method. These two nanomaterials were linked via boronic acid–diol covalent interaction by Lewis acid–base chemistry between phenylboronic acid based NIONPs and hydroxyl group functionalized CaCDs to develop NIONP-CaCD nanoconjugate. This blue emitting NIONP-CaCD conjugate was used in bioimaging and in pro-drug–free drug combination cancer therapy. Hydroxychloroquine (HCQ) was encapsulated within this NIONP-CaCD conjugate with a higher loading capacity in comparison to the individual cargo carrier (NIONPs or CaCDs). The disintegration of NIONP-CaCD conjugate to its native constituents took place through the cleavage of the boronate–diol bond at the lysosomal pH range (4.5–5.0), resulting in the liberation of HCQ and CaCDs. This pro-drug–free drug nanoformulation NIONP-CaCD-HCQ resulted in ∼3.0-fold improvement in cancer cell death in comparison to standalone therapy by individually loaded cargo. Notably, it also exhibited a ∼2.0-fold higher killing efficacy against cancer cells (A549 and HepG2) compared to normal cells (NIH3T3). This notable anticancer potential of NIONP-CaCD-HCQ could be attributed to Ca²⁺ overload induced apoptosis (calcicoptosis) in conjunction with lysosomal cell death by HCQ.