Radiolabeled Polymeric Nanoconstructs Loaded with Docetaxel and Curcumin for Cancer Combinatorial Therapy and Nuclear Imaging

Abstract

Growing evidence suggests that multifaceted diseases as cancer can be effectively tackled by hitting simultaneously different biological targets and monitoring patient‐specific responses. Combinatorial therapies, relying on the administration of two or more molecules with different cytotoxic mechanisms, are rapidly progressing in the clinic. Here, 100 nm spherical polymeric nanoconstructs (SPNs) are proposed for the combinatorial treatment of tumors by codelivering a potent antimitotic drug—docetaxel (DTXL)—and a broad spectrum anti‐inflammatory molecule—curcumin (CURC). In vitro, SPNs loaded with DTXL and CURC induce a threefold decrease in IC50 as compared to DTXL‐loaded SPNs. This synergic antitumor effect is also significant in mouse models of glioblastoma multiforme, where, after 22 d of treatment, the combinatorial approach leads to complete disease regression. At 90 d post‐treatment initiation, mice injected with DTXL + CURC SPNs have a 100% survival, whereas only 50% of the DTXL SPN treated mice survive. SPNs are also labeled with radioactive 64Cu(DOTA) molecules to document, via PET imaging, the progressive tumor mass shrinkage. Sensitization of DTXL by CURC is associated with NF‐κB downregulation and increased apoptosis. These theranostic nanoconstructs could be used for combinatorial treatment and assessment of therapeutic efficacy in other malignancies.

Organic nanoparticle systems for spatiotemporal control of multimodal chemotherapy

“…In addition, it sensitizes cancer cells to chemotherapeutic agents [67]. PLGA NP stabilized with a monolayer of phospholipids were used to co-deliver DTX and curcumin to treat glioblastoma [68]. Animals treated with the dual-drug NP showed complete tumor regression in 32 days from the initiation of treatment with 100% survival up to 90 days.…”

“…Animals treated with the dual-drug NP showed complete tumor regression in 32 days from the initiation of treatment with 100% survival up to 90 days. In contrast, tumors treated with DTX NP alone took one more week to show complete regression only to regrow a few weeks later [68]. Curcumin has also been combined with sorafenib in the treatment of hepatocellular carcinoma [67].…”

Integration of gadolinium in nanostructure for contrast enhanced‐magnetic resonance imaging

“…Zhang et al, 2007). To enhance the poor temporal resolution and sensitivity, CAs in the form of a nanoparticulate system has been used Aryal et al, 2017;Gizzatov et al, 2014;Jaehong Key et al, 2013;Jaehong Key et al, 2015;Lohrke et al, 2016;Pitchaimani et al, 2017;Pitchaimani et al, 2018;Stigliano, Key, Ramirez, Aryal, & Decuzzi, 2015). The main benefits of using nanoscale CAs is to provide a large contrast difference between tissues of interest with normal tissues by localizing CAs and minimize the Gd dose.…”

131I radiolabeled immune albumin nanospheres loaded with doxorubicin for in vivo combinatorial therapy

“…Furthermore, nanoconstructs can be engineered to deliver different therapeutic agents to a malignant mass simultaneously impacting multiple subcellular targets . In this respect, growing evidences suggest that combinatorial therapies, where conventional antitumor drugs are administered together with molecularly targeted agents, are more promising than traditional “one‐size‐fits‐all” therapeutic approaches . In 2016, Lin et al developed a radiation‐gene combinatorial therapy of hepatoma with radionuclide immune albumin nanospheres containing 131 I‐antiAFPMcAb and ganciclovir (GCV), which showed highly cellular uptake and selective affinity for AFP‐positive tumors …”

“…20 In this respect, growing evidences suggest that combinatorial therapies, where conventional antitumor drugs are administered together with molecularly targeted agents, are more promising than traditional "one-size-fits-all" therapeutic approaches. 21 In 2016, Lin et al developed a radiation-gene combinatorial therapy of hepatoma with radionuclide immune albumin nanospheres containing 131 I-antiAFPMcAb and ganciclovir (GCV), which showed highly cellular uptake and selective affinity for AFP-positive tumors. 22 Inspired by the above, we prepared a RIT and chemotherapy combinatorial therapy albumin nanospheres 131 I-antiAFPMcAb-DOX-BSA-NPs in this work (Scheme 1).…”