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Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer., Competing Interests: Declaration of competing interest The author declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

It remains challenging to develop an effective therapeutic agent for breast cancer. Synergistic therapies, particularly chemo-photothermal therapy, have gained increasing attention in cancer treatment. While the high working temperature achieved in photothermal therapy can kill tumor cells, it also causes thermal damage to nearby healthy cells, limiting the clinical application of chemo-photothermal synergistic therapy. To address these limitations, we have successfully synthesized nanoparticles by combining mesoporous polydopamine with atovaquone (ATO), denoted MPDA-ATO. These nanoparticles (NPs) enable chemo-photothermal therapy to be conducted at a mildly increased temperature of 46 °C. The MPDA-ATO NPs exhibit excellent photothermal stability, potent photothermal conversion properties, and good biocompatibility. In response to near-infrared radiation (NIR), MPDA-ATO can effectively kill 4T1 breast tumor cells in vitro and in the synergistic host. Furthermore, the MPDA-ATO NPs specifically inhibit STAT3, contributing to the antitumor effect. The treatment combining MPDA-ATO NPs with NIR could induce the apoptosis of tumor cells. In summary, the MPDA-ATO NPs offer improved efficacy and safety in treating breast cancer, providing insights and strategies for improved breast cancer therapy. [ABSTRACT FROM AUTHOR]

Aim: The development of a collaborative strategy with improved efficacy holds great promise in tumor treatment. This study aims to develop an effective collaborative strategy based on functionalized mesoporous polydopamine (MPDA) nanocomposites for killing tumor cells. Methods: MPDA nanoparticles were synthesized and functionalized with camptothecin (CPT) payload and manganese dioxide (MnO2) coating to construct MPDA-CPT-MnO2 nanocomposites. Results: When uptaken by tumor cells, the nanocomposites can degrade to produce O2, release CPT, and generate manganese (Mn2+) under the stimulation of hydrogen peroxide (H2O2) and acid. The released CPT and Mn2+ can act as chemotherapeutic drug and Fenton-like agent, respectively. Abundant reactive oxygen species (ROS) are generated in 4T1 tumor cells through an Mn2+-mediated Fenton-like reaction. After that, the generated Mn4+ can react with glutathione (GSH) through redox reaction to produce Mn2+ and deplete GSH, disrupting the reducing capacity and benefiting the production of ROS in tumor cells. Under laser irradiation, the nanocomposites can generate hyperthermia to promote the production of ROS. Conclusions: The developed MPDA-CPT-MnO2 nanocomposites can kill tumor cells through collaborative chemo/photothermal/chemodynamic therapy (CDT).

Hepatocellular carcinoma is a common and highly malignant disease. As a currently designated systemic chemotherapeutic agent for advanced Hepatocellular carcinoma, sorafenib has been confronted with dilemma of drug-resistance caused by tumor hypoxia, which hinders the therapeutic efficacy of the drug. Based on this, a multifunctional mesoporous polydopamine nanoprobe 2Me-SPIO-CY5.5@AAZ-MPDA with a mesoporous frame loaded 2-Methoxyestradiol, Superparamagnetic Iron Oxide Nanoparticles and the near-infrared dye cyanine 5.5, conjugated with hypoxia Hepatocellular carcinoma-specific targeting molecule of sulfonamides acetazolamide, is fabricated for hypoxic region targeting, sorafenib resistance reversion and photothermal therapy of Hepatocellular carcinoma. In addition, the magnetic resonance imaging/fluorescence/photoacoustic tri-modal imaging ability enables the tracing of the nanoprobes and monitoring the treatment procedure in vivo, providing a new methods of imaging-guided Hepatocellular carcinoma synergic treatment which improves the long-term therapeutic effects of sorafenib.

Photothermal therapy (PTT) is a promising method to kill pathogenic bacteria. However, using single-modal PTT, it is easy to cause tissue damage because of the overtemperature. Hence, it is necessary to combine PTT with other antibacterial strategies. In this study, we employed silver nanoparticles (Ag NPs) and mesoporous polydopamine (MPDA) nanoparticles to establish a multimodal antibacterial platform (MPDA@Ag). MPDA nanoparticles not only served as a photothermal transduction agent to convert light-energy to heat under the irradiation of near-infrared (NIR) light but also acted as a reducer to reduce Ag NPs in situ. Because Ag NPs can effectively kill bacteria, MPDA@Ag can overcome the drawbacks of the single-modal PTT antibacterial strategy, achieving a synergistic antibacterial effect. Moreover, as an antibiotic-free strategy, MPDA@Ag was less likely to induce drug resistance when killing bacteria. In summary, this platform offered a simple and practical means to achieve excellent antibacterial activity and supplied a good alternative to fight pathogenic bacteria. [ABSTRACT FROM AUTHOR]

The non-specific leakage of drugs from nanocarriers seriously weakened the safety and efficacy of chemotherapy, and it was very critical of constructing tumor microenvironment (TME)-responsive delivery nanocarriers, achieving the modulation release of drugs. Herein, using manganese dioxide (MnO2) as gatekeeper, an intelligent nanoplatform based on mesoporous polydopamine (MPDA) was developed to deliver doxorubicin (DOX), by which the DOX release was precisely controlled, and simultaneously the photothermal therapy (PTT) and chemodynamic therapy (CDT) were realized. In normal physiological environment, the stable MnO2 shell effectively avoided the leakage of DOX. However, in TME, the overexpressed glutathione (GSH) degraded MnO2 shell, which caused the DOX release. Moreover, the photothermal effect of MPDA and the Fenton-like reaction of the generated Mn2+ further accelerated the cell death. Thus, the developed MPDA-DOX@MnO2 nanoplatform can intelligently modulate the release of DOX, and the combined CDT/PTT/chemotherapy possessed high-safety and high-efficacy against tumors. [ABSTRACT FROM AUTHOR]

The high expression of reduced glutathione (GSH) and low pH in tumor sites have encouraged new ideas for targeted drug release. The tumor microenvironment is a crucial target for studying the anti-tumor efficiency of photothermal therapy because the microenvironment plays a key role in cancer progression, local resistance, immune escaping, and metastasis. Herein, active mesoporous polydopamine nanoparticles loaded with doxorubicin and functionalized with N,N′ -bis(acryloyl)cystamine (BAC) and cross-linked carboxymethyl chitosan (CMC) were used to induce simultaneous redox- and pH-sensitive activity to achieve photothermal enhanced synergistic chemotherapy. The inherent disulfide bonds of BAC were able to deplete glutathione, thus increasing the oxidative stress in tumor cells and enhancing the release of doxorubicin. Additionally, the imine bonds between CMC and BAC were stimulated and decomposed in the acidic tumor microenvironment, improving the efficiency of light conversion through exposure to polydopamine. Moreover, in vitro and in vivo investigations demonstrated that this nanocomposite exhibited improved selective doxorubicin release in conditions mimicking the tumor microenvironment and low toxicity towards non-cancerous tissues, suggesting there is high potential for the clinical translation of this synergistic chemo-photothermal therapeutic agent. [ABSTRACT FROM AUTHOR]

Polydopamine (PDA)-based Fenton agents attract increasing attention in tumor photothermal-enhanced chemodynamic therapy (CDT) due to their good biocompatibility and excellent loading capacity. However, PDA tends to eliminate the Fenton reaction-generated hydroxyl radical (∙OH) by its strong reducibility, which is an intractable hinder to the efficacy of CDT that need to be solved. Herein, a kind of mesoporous PDA-gold-manganese dioxide (MPDA-Au-MnO 2 , MPAM) nanoplatform was constructed for photothermal-enhanced CDT against tumor through the reducibility weakening strategy. The reducibility of original MPDA is effectively weakened by the oxidation role of HAuCl 4 and KMnO 4 during the preparation process, reducing the ∙OH scavenging ability of MPDA and benefiting the production of ∙OH. The MnO 2 shell could react with GSH to release Mn2+, acting as the Fenton-like agent to generate ∙OH. The exposed Au NPs can further deplete GSH through the Au-S bond interaction. MPDA acts as the photothermal agent to generate hyperthermia under laser irradiation. MPAM shows excellent intracellular GSH scavenging ability and enhanced ∙OH production ability. After intravenous injection, MPAM can significantly suppress the growth of tumors under laser irradiation, meanwhile showing good biosafety. The developed MPDA-based nanoplatform can not only display good potential in further tumor treatments but also provide meaningful enlightenment for developing high-performance PDA or MPDA-based nanoplatforms in CDT-related applications. [Display omitted] • A kind of mesoporous polydopamine-gold-manganese dioxide nanoplatform was formed. • The synthesis process could weaken the reducibility of mesoporous polydopamine. • Hydroxyl radical production was promoted through reducibility weakening strategy. • The formed nanoplatform displayed good photothermal performance. • Effective tumor elimination was achieved through photothermal-enhanced chemodynamic. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) combined with chemotherapy can break through the limitations of monotherapy and enhance the therapeutic efficacy. Polydopamine (PDA), an organic material with excellent photothermal conversion property and degradability, has broad application prospects in PTT. In this paper, PDA nanoparticles and mesoporous polydopamine (MPDA) nanoparticles were prepared with similar and uniform particle size to compare the photothermal performance, degradability, drug loading efficiency and release behavior. Polyethylene glycol (PEG) was coated on the surfaces of PDA and MPDA to boost their dispersion stability and biocompatibility. In vitro experimental results revealed that the two vehicles had satisfactory photothermal effect, drug storage capacity, and multi-responsive release properties of near-infrared (NIR) light /pH/H 2 O 2 /glutathione (GSH) for doxorubicin (DOX), while MPDA-PEG had superior photothermal performance, drug loading efficiency and longer-lasting release due to the mesoporous structure and higher surface area. Degradation experiments showed that MPDA degraded more quickly than PDA. The degradation behaviors of MPDA under different conditions were observed, and the possible degradation process was illustrated. Furthermore, the cell viability tests verified that DOX/MPDA-PEG had more eminent synergistic therapeutic effects in thermo-chemotherapy with a lower combination index (CI) of 0.313 compared with DOX/PDA-PEG (0.497). Therefore, MPDA has a broader application prospect for thermo-chemotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • The core of MPDA endowed nanoparticles with high drug loading characteristics. • The PDA shell of nanoparticles can achieve local and controlled drug release. • Surface-modified HA can mediate active tumor targeting of nanoparticles. • It realized the synergistic treatment of photothermal-chemotherapy. The combination of photothermal therapy (PTT) and chemotherapy is a promising strategy to overcome the shortcomings of monotherapy. For the first time, we designed a self-coated nanoparticle formed by mesoporous polydopamine (MPDA) core and polydopamine (PDA) shell, which was used to load docetaxel and modified with hyaluronic acid (HA). The obtained nanoparticle can achieve targeted drug delivery and further exert the synergistic effect of PTT and chemotherapy. The MPDA core has high drug loading due to mesopores, and the PDA shell can prevent the drug from releasing in the non-target-site because of the pH-sensitivity of the PDA. Compared with other PDA coated nanoparticle, self-coated nanoparticle has a simpler composition and can avoid the potential toxicity caused by the introduction of other materials. Experimental results showed that it had good photothermal conversion ability both in vivo and in vitro, and could be actively targeted into tumor cells through HA-mediated targeting. Under laser irradiation, it ablated the tumors. Simple ingredient and preparation, good compatibility and obvious therapeutic effect make it have a broad application prospect in tumor therapy. [ABSTRACT FROM AUTHOR]

Multifunctional nanodrugs integrating multiple therapeutic and imaging functions may find tremendous biomedical applications. However, the development of a simple yet potent theranostic nanosystem with a high payload and microenvironment responsiveness enhancing imaging‐guided cancer therapy is still a great challenge. Herein, a kind of MnCO‐entrapped mesoporous polydopamine nanoparticles are developed, which reach a 1.5 mg payload per gram carrier and exhibit marked theranostic capability through effective CO/Mn2+ generation and photothermal conversion inside the H+ and H2O2‐enriched tumor microenvironment, for a magnetic resonance/photoacoustic bimodal imaging‐guided tumor therapy. The multifunctional nanosystem exhibits a biocompatibility highly desirable for in vivo application and superior performance in inhibiting tumor growth and recurrence via combination CO and photothermal therapy. [ABSTRACT FROM AUTHOR]