Dual-Mode Avocado-like All-Iron Nanoplatform for Enhanced T1/T2 MRI-Guided Cancer Theranostic Therapy.

Development of T1/T2 dual-mode MRI contrast agents that can also treat cancer is an attractive prospect for personalized precision medicine. Unfortunately, conventional contrast agents can suffer from toxicity and lack any ability to treat cancer. An all-iron T1/T2 MR imaging agent with photothermal and drug delivery capability would overcome these issues. Here, an avocado-like Fe3+/Fe2O3 composed T1-T2 dual-mode contrast agent based on Fe-TA coordination network (CNMN) is developed. This material possesses suitable longitudinal and transverse relaxation coefficients. Moreover, the strong heat generation property of Fe-TA endows CNMN with the capability to act as a potent photothermal agent. Furthermore, CNMN can also act as an effective delivery platform for the chemotherapeutic drug doxorubicin (DOX) to achieve high effective chemo-photothermal combination therapy. The work demonstrates reliable T1-T2 MRI-guided chemo-photothermal therapy for safe and effective clinical application.

A pH-sensitive coordination polymer network-based nanoplatform for magnetic resonance imaging-guided cancer chemo-photothermal synergistic therapy.

Developing various kinds of nanoplatforms with integrated diagnostic and therapeutic functions would be significant for imaging-guided precision treatment of cancer. However, it is still a challenge to organically integrate therapeutic and imaging components into a single nano-system rather than simply mixing. Herein, an iron-gallic acid network-based nanoparticle (Fe-GA@PEG-PLGA) was designed for magnetic resonance imaging (MRI)-guided chemo-photothermal synergistic therapy of tumors. The tumor spatial location and size information can be accurately achieved due to T1 MRI based on Fe3+ coordination with GA in Fe-GA network. Furthermore, the nanoparticle exhibited extraordinary photostability and photothermal therapy capacity exceeded 42 °C within 100 s under 808 nm laser irradiation. Meanwhile, the Fe-GA polymeric network can be disassembled in tumor acidic environment and the released drug GA can induce apoptosis. This study demonstrated that the Fe-GA network-based nanoparticle is a promising diagnostic and therapeutic agent for theranostic application and further clinic translation.

CXCR4-Targeted and Redox Responsive Dextrin Nanogel for Metastatic Breast Cancer Therapy.

The unsatisfied results of cancer therapy are caused by many issues and metastasis of cancer cells is one of the major challenge. It has been reported that inhibiting the SDF1/CXCR4 interaction can significantly reduce the metastasis of breast cancer cells to regional lymph nodes and lung. Herein, a nanogel system equipped with the FDA-approved CXCR4 antagonist AMD3100 was developed and evaluated for its combined antimetastatic and tumor targeting effects. Briefly, a bioreducible cross-linked dextrin nanogel (DNG) coated with AMD3100 was designed to possess multiple functions, including CXCR4 chemokine targeting, inhibition of tumor metastasis, and reduction-responsive intracellular release of doxorubicin (DOX) to reduce the cells proliferation. The in vitro results confirmed that the DOX-loaded AMD3100-coated dextrin nanogel (DOX-AMD-DNG) was more effectively taken up by 4T1 breast cancer cells than DOX-DNG and was significantly more cytotoxic to 4T1 cells than DOX-DNG. In biodistribution studies, the stronger fluorescence intensity of Cy7-AMD-DNG than Cy7-DNG further confirmed that AMD3100 mediated tumor targeting in vivo. AMD3100-coated DOX-DNG also exhibited a distinct antimetastatic effect and CXCR4 antagonistic activity by inhibiting CXCR4-mediated cell invasion in 4T1 and U2OS cells. Moreover, DOX-AMD-DNG displayed superior anticancer activity and antimetastatic effects in orthotopic breast cancer-bearing Balb/C mice. In summary, the multifunctional DOX-AMD-DNG can effectively target the tumor site and dually impede cancer progression and metastasis.

Tumor-penetrating iron oxide nanoclusters for T1/T2 dual mode MR imaging-guided combination therapy.

Emerging nanotheranostic systems have promoted the development of dual-mode imaging techniques (i.e. T1/T2-weighted MRI) to meet the increasing requirements of accurate personalized treatment for cancer. Nevertheless, slight tumor accumulation and poor penetration have limited the efficacy of dual-mode theranostic agents. Furthermore, under the premise of guaranteeing imaging capability, most current research studies hardly focused on optimizing theranostic agents to achieve considerable therapeutic effects. Here, we developed a hyaluronic acid (HA)-stabilized iron oxide nanocluster (Fe2O3@PFDH NC) as an intelligent-degradable theranostic nanoagent for dual-mode MRI-guided chemo-photothermal therapy. The obtained Fe2O3@PFDH NC with high longitudinal and transverse relaxivities offers strong contrast in T1/T2-weighted MR imaging. Meanwhile, according to MR images, the intravenous Fe2O3@PFDH NC could accumulate at the hyaluronidase-rich tumor location gradually. More interestingly, it could break into smaller nanoparticles with quick DOX release for deep penetration, accompanied by highly effective photothermal ablation of the tumor under laser irradiation. In conclusion, the versatile tumor-penetrating Fe2O3@PFDH nanocluster could serve as a T1/T2 dual-mode MRI contrast agent with highly effective combination chemo-photothermal therapy, and would be an ideal theranostic nanocarrier with translational potential for future clinical diagnosis and treatment of cancer.

A nanoscale photothermal agent based on a metal-organic coordination polymer as a drug-loading framework for effective combination therapy.

Metallic materials are widely emerging as photothermal agents owing to their superior photothermal transduction efficiency and satisfactory photostability. In this study, an iron-based coordination polymer (Fe-CNP) loaded with doxorubicin (DOX) was assessed as a dual-function agent for photothermal therapy (PTT) and tumor-targeted chemotherapy. Fe-CNPs were synthesized by a one-step coordination reaction between Fe3+, hydrocaffeic acid, and dopamine-modified hyaluronic acid. A drug-loading method was developed to entrap DOX within Fe-CNPs through the formation of coordination bonds by Fe3+ and DOX (Scheme 1). DOX release was rapidly triggered in the cellular acidic environment and further enhanced by hyperpyrexia in the part of tumor, which will kill the remaining tumor cells after PTT. Animal experiments demonstrated complete inhibition of tumor growth without recurrence in 21 days after injection of DOX@Fe-CNPs with NIR laser irradiation. These results confirmed the enhanced anti-tumor efficiency of the chemo-photothermal nanosystem. Our work may reveal a photothermal coordination polymer as a drug-loading framework and highlight the development of metal-organic materials in combined chemo-photothermal therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT), which could directly act on tumors, has been considered as a promising treatment method for cancer. The combination of PTT with chemotherapy is attracting tremendous attention because such advanced application can achieve personalized precise medicine. Unfortunately, most PTT materials have photobleaching property, which results in reduced photothermal efficiency. Furthermore, their clinical applications also suffer from low loading capacity of chemotherapeutic drugs or nonbiodegradability in the biological system. In this study, we hypothesized that iron-based coordination polymers (Fe-CNPs) could function dually as agents to deliver both PTT and tumor-targeted chemotherapy by coordination loading of the chemotherapeutic drug doxorubicin (DOX). Our work may open up new avenues to rationally design versatile platforms for photothermal-chemotherapy to obtain synergistically enhanced therapeutic efficacy.