posted on 2024-02-15, 21:29authored byAnup Kumar Ghosh, Kathakoli Roy, Prasanta Kumar Das
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.