MRI-guided cell membrane-camouflaged bimetallic coordination nanoplatform for combined tumor phototherapy
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PROVIDER: S-EPMC10950690 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Project description:We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%-95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy.
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Project description:Currently, a large number of anti-tumor drug delivery systems have been widely used in cancer therapy. However, due to the molecular complexity and multidrug resistance of tumors, monotherapies remain suboptimal. Thus, this study aimed to develop a multifunctional theranostic nanoplatform for effective cancer therapy. Methods: Folic acid-modified silver sulfide@mesoporous silica core-shell nanoparticle was first modified with desthiobiotin (db) on the surface, then doxorubicin (DOX) was loaded into pore. Avidin was employed as "gatekeeper" to prevent leakage of DOX via desthiobiotin-avidin interaction. Db-modified survivin antisense oligonucleotide (db-DNA) which could inhibit survivin expression was then grafted on avidin at the outer layer of nanoparticle. DOX release and db-DNA dissociation were simultaneously triggered by overexpressing biotin in cancer cells, then combining PTT from Ag2S QD to inhibit tumor growth. Results: This nanoprobe had satisfactory stability and photothermal conversion efficiency up to 33.86% which was suitable for PTT. Due to the good targeting ability and fluorescent anti-bleaching, its signal still existed at the tumor site after tail vein injection of probe into HeLa tumor-bearing nude mice for 48 h. In vitro and in vivo antitumor experiments both demonstrated that drug, gene and photothermal synergistic therapy significantly enhanced antitumor efficacy with minimal systemic toxicity. Conclusion: Our findings demonstrate that this novel nanoplatform for targeted image-guided treatment of tumor and tactfully integrated chemotherapy, photothermal therapy (PTT) and gene therapy might provide an insight for cancer theranostics.
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Project description:Nanoparticles (NPs) modified by cell membranes represent an emerging biomimetic platform that can mimic the innate biological functions resulting from the various cell membranes in biological systems. researchers focus on constructing the cell membrane camouflaged NPs using a wide variety of cells, such as red blood cell membranes (RBC), macrophages and cancer cells. Cell membrane camouflaged NPs (CMNPs) inherit the composition of cell membranes, including specific receptors, antigens, proteins, for target delivering to the tumor, escaping immune from clearance, and prolonging the blood circulation time, etc. Combining cell membrane-derived biological functions and the NP cores acted cargo carriers to encapsulate the imaging agents, CMNPs are widely developed to apply in tumor imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), fluorescence imaging (FL) and photoacoustic imaging (PA). Herein, in this review, we systematically summarize the superior functions of various CMNPs in tumor imaging, especially highlighting the advanced applications in different imaging techniques, which is to provide the theoretical supports for the development of precise guided imaging and tumor treatment.
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Project description:Many cancer treatments including photodynamic therapy (PDT) utilize reactive oxygen species (ROS) to kill tumor cells. However, elevated antioxidant defense systems in cancer cells result in resistance to the therapy involving ROS. Here we describe a highly effective phototherapy through regulation of redox homeostasis with a biocompatible and versatile nanotherapeutic to inhibit tumor growth and metastasis. We systematically explore and exploit methylene blue adsorbed polydopamine nanoparticles as a targeted and precise nanocarrier, oxidative stress amplifier, photodynamic/photothermal agent, and multimodal probe for fluorescence, photothermal and photoacoustic imaging to enhance anti-tumor efficacy. Remarkably, following the glutathione-stimulated photosensitizer release to generate exogenous ROS, polydopamine eliminates the endogenous ROS scavenging system through depleting the primary antioxidant, thus amplifying the phototherapy and effectively suppressing tumor growth in vitro and in vivo. Furthermore, this approach enables a robust inhibition against breast cancer metastasis, as oxidative stress is a vital impediment to distant metastasis in tumor cells. Innovative, safe and effective nanotherapeutics via regulation of redox balance may provide a clinically relevant approach for cancer treatment.
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Project description:Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in the clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe3+ or Mn2+ ions as the cross-linker for cancer therapy. The combination index of two drugs is an essential parameter to evaluate drug combinations. The amphiphilic polymer poly(ethylene glycol)-block-polydopamine (PEG-PDA) was prepared by RAFT polymerization. The nanoparticles were prepared via self-assembly with Fe3+ or Mn2+ ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of the nanoparticles. The cell viability and combination index were evaluated in vitro. The tumor accumulation of the nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drug loading capacity. The drug loaded nanoparticles could kill cancer cells effectively with a combination index <1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition via intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application.
| S-EPMC6760993 | biostudies-literature
Project description:Two-dimensional transition metal carbides and nitrides (MXenes) nanosheets with high photothermal conversion efficiency as well as photothermal stability can efficiently generate remarkable hyperthermia for photothermal therapy (PTT) of cancer. However, mono-MXenes cannot exhibit precise diagnosis and treatment to complete ablation of cancer cells in the PTT process. To overcome this dilemma, an "all-in-one" nanoplatform of titanium carbide (Ti3C2) MXene-based composite nanosheets is developed for magnetic resonance imaging (MRI)-guided multi-modal hyperthermia and chemodynamic tumor ablation, which was achieved by bonding of manganese ion on the surface of Ti3C2, and then was the functionalized nanosheets was modified by biocompatible PEG (Mn-Ti3C2@PEG). Due to magnetic and Fenton-like catalytic properties of Mn components, Mn-Ti3C2@PEG not only acted as the contrast agents for T1-weighted MRI (relaxivity value of 1.05 mM-1 s-1), but also converted cellular H2O2 into highly toxic hydroxyl radicals (·OH) mediated chemodynamic therapy (CDT). Moreover, Furthermore, Mn-Ti3C2@PEG can efficiently suppressed tumor-growth by PTT, due to the high photothermal conversion capability and photothermal stability. As a proof-of-concept model, the as-designed Mn-Ti3C2@PEG nanoplatform shows simultaneous MRI and dual-modal treatment for effective suppression of tumor with minimized side effects both in vitro and in vivo, indicating the great potential for clinical cancer theranostics.
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Project description:Photoacoustic imaging and photothermal therapy that employ organic dye in the second near-infrared window (NIR-II) became an attractive theranostical strategy for eliminating solid tumors, in which IR1048 was previously reported to be a good candidate. However, the further biomedical application of IR1048 was blocked by its poor water-solubility and lack of tumor-targeting. To solve this problem, liposome camouflaged with 4T1 cell membrane fragments was employed to encapsulate IR1048 (thereafter called MLI), and its application for photoacoustic and thermo-imaging and photothermal therapy were explored in vitro and in vivo. The results showed that MLI exhibited spherical morphology around 92.55 ± 5.41 nm coated by monolayer adventitial fragments, and uniformly dispersed in PBS with high loading efficiency and encapsulation efficiency to IR1048. In addition, both free IR1048 and MLI presented strong absorption in NIR-II, and upon 1064 nm laser irradiation the MLI showed awesome photothermal performance that could rapidly elevate the temperature to 50.9 °C in 6 min. Simultaneously, phantom assay proved that MLI could dramatically enhance the photoacoustic amplitudes by a linear concentration-dependent way. Moreover, either flow cytometry or confocal analysis evidenced that MLI was the most uptaked by 4T1 cells among other melanoma B16 cells and Hek293 cells and coexist of IR1048 and 1064 nm laser irradiation were indispensable for the photothermal cytotoxicity of MLI that specifically killed 96.16% of 4T1 cells far outweigh the B16 cells while hardly toxic to the Hek293 normal cells. Furthermore, PA imaging figured out that 4 h post tail-vein injection of MLI was the best time to give 1064 nm irradiation to conduct the photothermal therapy when the average tumor-accumulation of MLI achieved the highest. In the NIR-II photothermal therapy, MLI could significantly inhibit the tumor growth and almost ablated the tumors with slight body weight variation and the highest average life span over the therapy episode and caused no damage to the normal organs. Hence, MLI could pave the way for further biomedical applications of IR-1048 by homologous tumor-targeting and dual-modal imaging directed NIR-II accurate photothermal therapy with high efficacy and fine biosafety.
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Project description:Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.
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