TY - JOUR
T1 - Transforming Small-Molecule Nanoaggregation into Functional Drug Delivery Platforms
AU - Kim, Jun Hyuk
AU - Kulthe, Arun Dattatray
AU - Park, Su Jeong
AU - Raj, Vinit
AU - Lee, Woo Ram
AU - Nimse, Satish Balasaheb
N1 - Publisher Copyright:
© 2025 American Chemical Society.
PY - 2025/5/22
Y1 - 2025/5/22
N2 - The development of stimuli-responsive nanoaggregates offers a transformative approach to cancer therapy, addressing the challenges of selectivity and efficacy. The spontaneous formation of nanoscale aggregates of small organic molecules through self-assembly is a major hurdle in early-stage drug discovery. However, this disadvantage can be transformed with a meticulous design into a functional drug delivery platform. Here, we report Nano-CC1-Acl, a nanoaggregate engineered for targeted anticancer activity. CC1 and CC1-Acl, benzimidazole derivatives, undergo self-assembly in aqueous environments to generate Nano-CC1 (235.2 ± 28.2 nm; IC50 > 100 μM) and Nano-CC1-Acl (110.6 ± 23.1 nm; IC50 = 2.88-3.40 μM) nanoaggregates. The IC50 value of Nano-CC1-Acl further decreases to 0.20 ± 0.16 μM in the presence of cysteine, a biothiol. Triggered by intracellular biothiols, Nano-CC1-Acl disassembles to release CC1, a potent microtubule-targeting agent that disrupts microtubule polymerization. Results presented here indicate that small molecule nanoaggregation can be utilized to develop functional drug delivery platforms.
AB - The development of stimuli-responsive nanoaggregates offers a transformative approach to cancer therapy, addressing the challenges of selectivity and efficacy. The spontaneous formation of nanoscale aggregates of small organic molecules through self-assembly is a major hurdle in early-stage drug discovery. However, this disadvantage can be transformed with a meticulous design into a functional drug delivery platform. Here, we report Nano-CC1-Acl, a nanoaggregate engineered for targeted anticancer activity. CC1 and CC1-Acl, benzimidazole derivatives, undergo self-assembly in aqueous environments to generate Nano-CC1 (235.2 ± 28.2 nm; IC50 > 100 μM) and Nano-CC1-Acl (110.6 ± 23.1 nm; IC50 = 2.88-3.40 μM) nanoaggregates. The IC50 value of Nano-CC1-Acl further decreases to 0.20 ± 0.16 μM in the presence of cysteine, a biothiol. Triggered by intracellular biothiols, Nano-CC1-Acl disassembles to release CC1, a potent microtubule-targeting agent that disrupts microtubule polymerization. Results presented here indicate that small molecule nanoaggregation can be utilized to develop functional drug delivery platforms.
UR - https://www.scopus.com/pages/publications/105004025988
U2 - 10.1021/acs.jmedchem.5c00562
DO - 10.1021/acs.jmedchem.5c00562
M3 - Article
C2 - 40314125
AN - SCOPUS:105004025988
SN - 0022-2623
VL - 68
SP - 10384
EP - 10398
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 10
ER -
