Carrier‐Free Nanoassembly of Curcumin–Erlotinib Conjugate for Cancer Targeted Therapy

Abstract

Anticancer drug-loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, nonstandardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved for clincial use. Herein, a carrier-free nanoparticle based on the self-assembly of the curcumin-erlotinib conjugate (EPC) is developed. The EPC nanoassembly exhibits more potent cell killing, better antimigration, and anti-invasion effects for BxPC-3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefiting from both passive and active tumor targeting effect, EPC nanoassembly can effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduces the growth of pancreatic tumors and extends the median survival time of the tumor-bearing mice from 22 to 68 days. In addition, no systemic toxicity is detected in the mice receiving EPC treatment. Attributed to the uniformity of the curcumin-erlotinib conjugate and easiness of scaling up, it is expected that the EPC can be translated into a powerful tool in fighting against pancreatic cancer and other epidermal growth factor receptor positive cancers.

Receptor Tyrosine Kinases and Their Signaling Pathways as Therapeutic Targets of Curcumin in Cancer

“…These components are involved in erlotinib-resistance, and the addition of curcumin to erlotinib treatment seems to influence associated drug resistance signaling pathways. An erlotinib and curcumin conjugated carrier-free nanoassembly (EPC) was also developed and found to have better tumour-penetrating and anti-migratory properties in addition to the absence of systemic toxicity ( Cheng et al, 2020 ). Lastly, combinations of curcumin and lapatinib were also found to increase lapatinib-induced inhibition of the Her2-Akt pathway, reverse lapatinib resistance and decrease metastatic potential in breast cancer cells ( Liu et al, 2015 ; Saxena et al, 2020 ).…”

Curcumin: reclaiming the lost ground against cancer resistance

“…The concerns regarding poor water solubility (0.6 μg/mL) have been addressed through various methods to increase the bioavailability for in vivo studies. Successful efforts have been made through preparation of various formulations like nanoparticles [110][111][112][113] , liposomes [114,115] and combinatorial treatment [116][117][118][119] of curcumin with anticancer agents. It is important to note that free curcumin has also shown commendable activity during in vivo studies despite its limitations of lower water solubility, stability and bioavailability but the formulated curcumin or curcumin in combinatorial treatment has exceeded the performance of isolated treatment of free curcumin in majority of the cases.…”

Research Progress of Carrier-Free Antitumor Nanoparticles Based on Phytochemicals

“…In addition, apoptosis during Cur-based photodynamic therapy is accompanied by ROS-mediated activation of the JNK/caspase-3 signaling pathway. In addition to self-assembly of Cur molecules, Cheng et al (Cheng et al, 2020) designed carrierfree nanoparticles based on a curcumin-erlotinib conjugate (EPC), with a size of approximately 105 nm and a hydrodynamic size of 146.3 nm with a PDI of 0.157. Compared with free Cur and erlotinib, EPCs have stronger cytotoxicity and better anti-migration and anti-invasion effects on BxPC-3 pancreatic cancer cells.…”