Ferrocene‐Based Polymeric Nanoparticles Carrying Doxorubicin for Oncotherapeutic Combination of Chemotherapy and Ferroptosis

Abstract

Mono‐chemotherapy has significant side effects and unsatisfactory efficacy, limiting its clinical application. Therefore, a combination of multiple treatments is becoming more common in oncotherapy. Chemotherapy combined with the induction of ferroptosis is a potential new oncotherapy. Furthermore, polymeric nanoparticles (NPs) can improve the antitumor efficacy and decrease the toxicity of drugs. Herein, a polymeric NP, mPEG‐b‐PPLGFc@Dox, is synthesized to decrease the toxicity of doxorubicin (Dox) and enhance the efficacy of chemotherapy by combining it with the induction of ferroptosis. First, mPEG‐b‐PPLGFc@Dox is oxidized by endogenous H2O2 and releases Dox, which leads to an increase of H2O2 by breaking the redox balance. The Fe(II) group of ferrocene converts H2O2 into ·OH, inducing subsequent ferroptosis. Furthermore, glutathione peroxidase 4, a biomarker of ferroptosis, is suppressed and the lipid peroxidation level is elevated in cells incubated with mPEG‐b‐PPLGFc@Dox compared to those treated with Dox alone, indicating ferroptosis induction by mPEG‐b‐PPLGFc@Dox. In vivo, the antitumor efficacy of mPEG‐b‐PPLGFc@Dox is higher than that of free Dox. Moreover, the loss of body weight in mice treated mPEG‐b‐PPLGFc@Dox is lower than in those treated with free Dox, indicating that mPEG‐b‐PPLGFc@Dox is less toxic than free Dox. In conclusion, mPEG‐b‐PPLGFc@Dox not only has higher antitumor efficacy but it reduces the damage to normal tissue.

Recent progress in biomaterials-driven ferroptosis for cancer therapy

“…Lin et al designed a polymer, mPEG- b -PPLGFc@Dox, to enhance anticancer efficacy and reduce drug toxicity through chemotherapy combined with ferroptosis. 104 He et al developed semiconductor polymer nanoparticles with iron chelation (SPFeN), where Fe 3+ acted as a ferroptosis inducer. SPFeN generated hydroxyl radicals inducing ferroptosis and synergistically accelerated Fenton reaction for photothermal therapy, ultimately achieving optimal tumour inhibition.…”

Photothermal‐enhanced in situ supramolecular hydrogel promotes bacteria‐infected wound healing in diabetes

“…10 As is well known, the hydroxyl radicals (•OH) could be efficiently obtained through the Fenton reaction, in which the H 2 O 2 could be converted to •OH in the presence of Fe 2þ . 11 Moreover, H 2 O 2 could be found in the inflammatory microenvironment, especially in the diabetic wound. The high blood sugar microenvironment of a diabetic wound causes bacteria to grow faster than in a normal wound and also prevents the immune system from killing invading bacteria.…”

“…As is well known, the hydroxyl radicals (·OH) could be efficiently obtained through the Fenton reaction, in which the H 2 O 2 could be converted to ·OH in the presence of Fe 2+ 11 . Moreover, H 2 O 2 could be found in the inflammatory microenvironment, especially in the diabetic wound.…”

Synthesis of Fe3O4 core/MIL-100(Fe) shell nanocomposites for tumor chemo-ferroptosis combination therapy and MR imaging

“…However, solely relying on chemotherapy as a treatment option falls short in delivering desirable therapeutic outcomes due to the absence of tumor-specific targeting, detrimental effects on healthy tissues, and the escalating issue of multidrug resistance [1,2]. Hence, in order to improve the tumor treatment efficiency, researchers are working towards developing a combination of chemotherapy and other therapeutic modalities [3][4][5][6][7][8][9][10][11][12][13][14][15]. For example, in clinical practice, combining radiotherapy and chemotherapy has shown promising results in reducing recurrence rate and extending survival time for patients affected with tumors like rectal cancer, nasopharyngeal cancer, gastric cancer, and esophageal cancer [16][17][18][19].…”