Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic‐Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport

Abstract

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti‐tumor treatment. In addition, central nervous system neoplasm‐targeted nanoplatforms are urgently required. To address these issues, a new multi‐functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP‐TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione‐responsive disulfide bond. Mechanistically, ODP‐TH crosses the blood–brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down‐regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia‐inducible factor‐1‐α (HIF‐1α). The results reveal that ODP‐TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP‐TH achieves a more efficient tumor‐inhibiting effect. This study not only overcomes the hypoxia‐related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi‐functional targeted and intensive anti‐tumor nanoplatform.

How Nanotherapeutic Platforms Play a Key Role in Glioma? A Comprehensive Review of Literature

“…It downregulates the expression of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1α (HIF-1α), resulting in improved therapeutic outcomes. 194 Hydrogel Hydrogels, which are water-soluble, three-dimensional polymer networks, have garnered significant interest in recent years due to their tunable physicochemical properties. 195 The hydrophilic functional groups attached to the polymer backbone facilitate water absorption and retention, while cross-linking between the polymer chains ensures their stability in an aqueous environment.…”

Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer

“…21 Using Hb to elevate the oxygen concentration within tumors, this combination therapy approach enhances the effectiveness of anti-tumor treatments. 22,23 However, few researchers have explored the simultaneous elevation of O 2 levels and increased ROS within cancer cells to improve therapeutic outcomes. Therefore, there is an urgent need to develop novel combination therapies to enhance the efficacy of catalytic treatments.…”

Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor

“…17 Recently, many strategies have been developed for enhancing the oxygen concentration in tumors by directly delivering oxygen using hemoglobin, perfluorocarbons, and metal–organic frameworks, or by decomposing solid peroxides to generate oxygen. 18–20 However, most oxygen carriers used in these strategies are non-biodegradable, thus may cause side effects, and the purity and solubility of solid peroxide can significantly impact oxygen generation. Another strategy for improving the oxygen content in tumors is the in situ catalytic decomposition of endogenous H 2 O 2 to produce O 2 by using catalase (CAT).…”