Degradable Carrier-Free Metal–Phenolic Network Theranostic Agent with Targeted Mitochondrial Damage for Efficient Cancer Theranostics

Abstract

Mitochondria-targeted cancer therapy holds great promise for anticancer treatments. It is thus of great significance to explore effective strategies for targeted mitochondrial damage in cancer cells. Herein, a degradable carrier-free curcumin-based metal−phenolic network (MPN) theranostic agent, namely, the indocyanine green-loaded curcumin−Gd nanoparticle (ICG@cur-Gd NP), is reported for magnetic resonance (MR)/ fluorescence dual-modal imaging-guided chemo-/photodynamic combination cancer therapy. The ICG@cur-Gd NPs are fabricated by coordination-driven self-assembly of curcumin and Gd 3+ , followed by ICG loading. This theranostic agent intrinsically enables the MR and fluorescence imaging for real-time tumor visualization and precise guidance during anticancer treatments. Tumor-acidity-responsive degradation of ICG@cur-Gd NPs induces tumor-specific release of curcumin, ICG, and Gd 3+ with no long-term systemic toxicity. The results reveal that the curcumin component of ICG@cur-Gd NPs can induce efficient mitochondrial damage. The excellent anticancer efficacy of ICG@cur-Gd NPs with laser exposure is confirmed in vivo, highlighting its potential for clinical use. This study constitutes the first report of a curcumin-based MPN theranostic agent combined with the clinically approved and used MR imaging contrast agent Gd 3+ . This work provides a novel and efficient strategy to construct carrier-free theranostic agents for imaging-guided cancer theranostics.

Biodegradable Amorphous Copper Iron Tellurite Promoting the Utilization of Fenton-Like Ions for Efficient Synergistic Cancer Theranostics

“…Thus, the low atomic utilization efficiency of chemodynamic agents discounts the therapeutic efficacy of CDT. Another challenge limiting the CDT efficiency is the glutathione (GSH)-related cellular antioxidant defense system. − The high concentration of GSH (1–10 mM) leads to the elimination of •OH from the tumor microenvironment (TME), also deteriorating the •OH-mediated CDT treatment. , Additionally, the majority of inorganic chemodynamic agents previously reported are nonbiodegradable substances with long-term body retention, thus exerting potential biosafety issues and adverse biological effects. , Although renal clearable ultrasmall nanomaterials (<6 nm) could mitigate the long-term body retention issues, it would decrease the tumor accumulation due to the weakened enhanced permeability and retention (EPR) effect. , To address these issues, numerous efforts have been devoted to TME-degradable chemodynamic agents for efficient CDT treatment of cancer. ,− However, the use of TME-responsive chemodyamic agents is mainly limited to the release of embedded metal ions or partial degradation with drug carriers still retained in the body over a prolonged period of time. Therefore, it is highly imperative to develop body-clearable, TME-degradable chemodynamic agents without compromising the therapeutic efficacy for efficient anticancer treatment.…”

Research progress on self-assembled nanodrug delivery systems

“…This study provides a novel and effective strategy for the construction of a vector free therapeutic agent for image-guided cancer therapy. 107 Dai et al designed polyphenol nanocomposites as E100 nm PEGylated nanoparticles containing Pt prodrugs (PTP NPs) for cancer treatment. The rapid emulsion-based co-assembly process for the PTP NP components with multifunctional synthesis of polyphenols conjugated to Pt(IV) precursor drugs, peg, or NPs within 1 h. A PTP imaging agent can be mediated by cell internalization, and a quaternary Pt precursor drug is reduced by second-order cisplatin cells, leading to apoptosis.…”

“…This study provides a novel and effective strategy for the construction of a vector free therapeutic agent for image-guided cancer therapy. 107…”

Autocatalytic oncotherapy nanosystem with glucose depletion for the cascade amplification of hypoxia-activated chemotherapy and H2O2-dependent chemodynamic therapy

“…[33][34][35][36] In this regard, synergistic therapy strategies integrating two or more therapeutic modalities into a platform are very desirable because of their high potential to improve the therapeutic efficacy in tumor treatment. [37][38][39][40] It is well known that tumor cells rely more heavily on glucose to maintain their survival and growth due to the rapid metabolism and proliferation compared with normal cells. 41,42 Therefore, tumor cells are very susceptible to changes in glucose concentration.…”

“…33–36 In this regard, synergistic therapy strategies integrating two or more therapeutic modalities into a platform are very desirable because of their high potential to improve the therapeutic efficacy in tumor treatment. 37–40…”