Theranostic Potential of Metal-Organic Framework/Polydopamine-Modified Magnetic Nanoparticles for Photothermal/Chemotherapy and MR Imaging.

Personalized strategies for delivering photo therapies to solid tumors with theranostic nanoparticles (Conference Presentation)

The combination of multidrug chemotherapy and photothermal therapy (PTT) enhances cancer therapeutic efficacy. Herein, we develop a simple and smart pH/NIR dual-stimulus-responsive degradable mesoporous CoFe2O4@PDA@ZIF-8 sandwich nanocomposite. The mesoporous CoFe2O4 core acts as T2-weighted magnetic resonance (MR) imaging probe, PTT agent, and loading platform of hydrophilic doxorubicin (DOX). A polydopamine (PDA) layer is used to avoid the premature leakage of DOX before arriving at tumor site, enhance PTT efficiency, and facilitate the integration of ZIF-8 (a kind of metal-organic framework). The ZIF-8 shell serves to encapsulate hydrophobic camptothecin (CPT) and as the switch for the pH and NIR stimulation-responsive release of the two drugs. Therefore, T2-weighted MR imaging-guided multidrug chemotherapy and PTT synergistic treatment is achieved. Two kinds of anticancer drugs, hydrophilic DOX and hydrophobic CPT, are successfully loaded in CoFe2O4 and ZIF-8, respectively, so no mutual interference between the two drugs exists. A unique two-stage stepwise release process is exhibited for CPT and DOX with an interval of 12 h to improve the anticancer efficacy under the acidic microenvironment of tumor tissue. NIR irradiation achieves the burst drug-release and PTT after laser stimulation, simultaneously. With this smart design, high drug concentration is achieved at the tumor site by quick release, especially for the therapeutic drugs that show nonlinear pharmacokinetics, and PTT is integrated efficiently. Furthermore, negligible biotoxicity and a remarkable synergic antitumor effect of the hybrid nanocomposites are validated by HepG2 cells and tumor-bearing mice as models. Our multidrug delivery-releasing composite improves tumor therapeutic efficiency significantly compared with a single-drug chemotherapy system. The simple multifunctional composite system can be applied as an effective platform for personal nanomedicine with diagnosis, smart drug delivery, and cancer treatment through its remarkable photothermal property and controllable multidrug release.

Multidrug-resistant (MDR) bacteria are rapidly emerging, coupled with the failure of current antibiotic therapy; thus, new alternatives for effectively treating infections caused by MDR bacteria are required. Hyperthermia-mediated photothermal therapy (PTT) and reactive oxygen species (ROS)-mediated photodynamic therapy (PDT) have attracted extensive attention as antibacterial therapies owing to advantages such as low invasiveness, low toxicity, and low likelihood of causing bacterial resistance. However, both strategies have notable drawbacks, including the high temperature requirements of PTT and the weak ability of PDT-derived ROS to penetrate target cells. To overcome these limitations, a combination of PTT and PDT has been used against MDR bacteria. In this review, we discuss the unique benefits and limitations of PTT and PDT against MDR bacteria. The mechanisms underlying the synergistic effects of the PTT-PDT combination are also discussed. Furthermore, we introduced advancements in antibacterial methods using nano-based PTT and PDT agents to treat infections caused by MDR bacteria. Finally, we highlight the existing challenges and future perspectives of synergistic PTT-PDT combination therapy against infections caused by MDR bacteria. We believe that this review will encourage synergistic PTT- and PDT-based antibacterial research and can be referenced for future clinical applications.

Chemotherapy remains restricted by its toxic adverse effects and resistance to drugs. The treatment of nitric oxide (NO) combined with imaging-guided physical therapy is a promising alternative for clinical applications. Herein, we report nanoscale metal-organic framework (NMOF) systems to integrate magnetic resonance (MR) imaging, spatiotemporally controllable NO delivery, and photothermal therapy (PTT) as a new means of cancer theranostics. As a proof of concept, the NMOFs are prepared with biocompatible Zr4+ ions and Mn-porphyrin as a bridging ligand. By inserting paramagnetic Mn ions into porphyrin rings, Mn-porphyrin renders the NMOFs strong T1-weighted MR contrast capacity and high photothermal conversion for efficient PTT. S-Nitrosothiol (SNO) is conjugated to the surfaces of the NMOFs for heat-sensitive NO generation. Moreover, single near-infrared (NIR) light triggers the controllable NO release and PTT simultaneously for their efficient synergistic therapy with one-step operation. Upon intravenous injection, NMOF-SNO shows effective tumor accumulation as exposed by the MR images of the tumor-bearing mice. When exposed to the NIR laser, the tumors of mice injected with NMOF-SNO are completely inhibited, verifying the efficiency of NMOF-SNO. For the first time, Mn-porphyrin NMOFs are developed to be an effective theranostic system for MR imaging-guided controllable NO release and photothermal synergetic therapy under single NIR irradiation.

Metal-organic frameworks (MOFs) have been identified as promising materials for the delivery of therapeutics to cure cancer owing to their intrinsic porous structure. However, in a majority of cases, MOFs act as only a delivery cargo for anticancer drugs while little attention has been focused on the utilization of their intriguing physical and chemical properties for potential anticancer purposes. Herein for the first time, an ultrathin (16.4 nm thick) ferrocene-based MOF (Zr-Fc MOF) nanosheet has been synthesized for synergistic photothermal therapy (PTT) and Fenton reaction-based chemodynamic (CDT) therapy to cure cancer without additional drugs. The Zr-Fc MOF nanosheet acts not only as an excellent photothermal agent with a prominent photothermal conversion efficiency of 53% at 808 nm but also as an efficient Fenton catalyst to promote the conversion of H2O2 into hydroxyl radical (•OH). As a consequence, an excellent therapeutic performance has been achieved in vitro as well as in vivo through this combinational effect. This work aims to construct an "all-in-one" MOF nanoplatform for PTT and CDT treatments without incorporating any additional therapeutics, which may launch a new era in the investigation of MOF-based synergistic therapy platforms for cancer therapy.

BackgroundPeriodontitis is a chronic inflammatory disease in oral cavity owing to bacterial infection. Photothermal therapy (PTT) and photodynamic therapy (PDT) have many advantages for antibacterial treatment. As an excellent photosensitizer, indocyanine green (ICG) shows prominent photothermal and photodynamic performances. However, it is difficult to pass through the negatively charged bacterial cell membrane, thus limiting its antibacterial application for periodontitis treatment.ResultsIn this work, self-assembled nanoparticles containing ICG and polycationic brush were prepared for synergistic PTT and PDT against periodontitis. First, a star-shaped polycationic brush poly(2-(dimethylamino)ethyl methacrylate) (sPDMA) was synthesized via atom transfer radical polymerization (ATRP) of DMA monomer from bromo-substituted β-cyclodextrin initiator (CD-Br). Next, ICG was assembled with sPDMA to prepare ICG-loaded sPDMA (sPDMA@ICG) nanoparticles (NPs) and the physicochemical properties of these NPs were characterized systematically. In vitro antibacterial effects of sPDMA@ICG NPs were investigated in porphyromonas gingivalis (Pg), one of the recognized periodontitis pathogens. A ligature-induced periodontitis model was established in Sprague–Dawley rats for in vivo evaluation of anti-periodontitis effects of sPDMA@ICG NPs. Benefiting from the unique brush-shaped architecture of sPDMA polycation, sPDMA@ICG NPs significantly promoted the adsorption and penetration of ICG into the bacterial cells and showed excellent PTT and PDT performances. Both in vitro and in vivo, sPDMA@ICG NPs exerted antibacterial and anti-periodontitis actions via synergistic PTT and PDT.ConclusionsA self-assembled nanosystem containing ICG and polycationic brush has shown promising clinical application for synergistic PTT and PDT against periodontitis.Graphical

A photosensitizer-loaded zinc oxide-polydopamine core-shell nanotherapeutic agent for photodynamic and photothermal synergistic therapy of cancer cells

In this study, we introduce a novel nanoplatform, polypyrrole (PPy)‐2,2′‐Azobis[2‐(2‐imidazolin‐2‐yl)propane] dihydrochloride (AIPH)@lauric acid (LA) (PPy‐AIPH@LA) nanoparticles (NPs), designed to overcome these limitations through synergistic photothermal therapy (PTT) and photodynamic therapy (PDT). This dual‐responsive system incorporates PPy for efficient photothermal conversion, AIPH for thermos‐responsive and oxygen‐independent free radical generation, and LA as a thermally responsive encapsulation layer. The LA coating melts upon 808 nm near‐infrared laser irradiation, releasing AIPH and free radicals to enable precise spatiotemporal activation of therapeutic effects. PPy‐AIPH@LA demonstrates exceptional photothermal conversion efficiency (55.74%) and generates sufficient radicals to enhance PDT efficacy, even in hypoxic tumor microenvironments. In vitro studies revealed concentration‐dependent tumor cell ablation and inhibition of migration, while in vivo experiments showed that the combined PTT‐PDT treatment achieved an impressive 90.7% tumor growth inhibition rate in a mouse colon cancer cells CT‐26 murine model, with no significant systemic toxicity. Molecular analyses further revealed modulations in pathways associated with tumor metabolism, apoptosis, and immune escape, highlighting the comprehensive therapeutic potential of this nanoplatform. These findings underscore the potential of PPy‐AIPH@LA as a safe, effective, and minimally invasive nanotherapeutic platform for combating CRC and other solid tumors.

The development of a simple and effective single constituent multifunctional nanotheranostic platform producing a multimodality diagnostic signal and curing effect is still a challenge. Herein, we synthesized simple and biodegradable FeWOx ternary oxide nanoparticles and modified their surface with RGD-PEG-NH2 (FeWOx-PEG-RGD NPs), whereby resulting NPs possessed a (T2/T1) switchable MRI/CT dual-modal imaging ability and synergistic photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT) capacity. We showed that FeWOx-PEG-RGD NPs enabled tumor accumulation under a magnetic field drive and RGD-mediated tumor penetration and implemented PTT/PDT treatment under 980 nm laser irradiation. In an acidic tumor microenvironment (TME) with a high hydrogen peroxide (H2O2) expression, NPs degraded to release Fe3+ and Fe2+, triggering a Fenton reaction to generate ˙OH for CDT. The released Fe2+ led to T2/T1 signal conversion for tracing cancer therapy, while the high X-ray attenuation coefficient of W also made it a good CT contrast agent for guided therapy. Thus, the structurally simple FeWOx-PEG-RGD was capable of mediating (T2/T1-weighted) MR/CT two modal imaging-guided PTT/PDT/CDT synergic therapy with a high accuracy and superb anticancer efficiency. The simple, degradable, rapid-clearance, and multifunctional FeWOx-PEG-RGD NPs provide a novel, promising, and versatile nanotheranostic platform.

A high-sensitivity and low-power theranostic nanosystem that combines with synergistic photothermal therapy and surface-enhanced Raman scattering (SERS) mapping is constructed by mesoporous silica self-assembly on the reduced graphene oxide (rGO) nanosheets with nanogap-aligned gold nanoparticles (AuNPs) encapsulated and arranged inside the nanochannels of the mesoporous silica layer. Rhodamine 6G (R6G) as a Raman reporter is then encapsulated into the nanochannels and anti-epidermal growth factor receptor (EGFR) is conjugated on the nanocomposite surface, defined as anti-EGFR-PEG-rGO@CPSS-Au-R6G, where PEG is polyethylene glycol and CPSS is carbon porous silica nanosheets. SERS spectra results show that rGO@CPSS-Au-R6G enhances 5 × 10(6) magnification of the Raman signals and thus can be applied in the noninvasive cell tracking. Furthermore, it displays high sensitivity (detection limits: 10(-8) m R6G solution) due to the "hot spots" effects by the arrangements of AuNPs in the nanochannels of mesoporous silica. The highly selective targeting of overexpressing EGFR lung cancer cells (A549) is observed in the anti-EGFR-PEG-rGO@CPSS-Au-R6G, in contrast to normal cells (MRC-5). High photothermal therapy efficiency with a low power density (0.5 W cm(-2) ) of near-infrared laser can be achieved because of the synergistic effect by conjugated AuNPs and rGO nanosheets. These results demonstrate that the anti-EGFR-PEG-rGO@CPSS-Au-R6G is an excellent new theranostic nanosystem with cell targeting, cell tracking, and photothermal therapy capabilities.

Gold nanoparticle-coated thermosensitive liposomes for the triggered release of doxorubicin, and photothermal therapy using a near-infrared laser

Photothermal therapy (PTT) is a powerful technique for tumor ablation. However, there is a problem that PTT cannot accurately locate the tumor site, so it is easy to cause heat damage to the surrounding normal tissues. In this study, PEGylated amorphous manganese dioxide (MnO₂) coated polydopamine (PDA) core-shell nanoparticles (PDA@MnO₂-PEG) with regular morphology and uniform dimensions were prepared for acid-sensitive magnetic resonance imaging-guided tumor photothermal therapy. The results showed that amorphous MnO₂ shell provided markedly acid-sensitive T1-weighted magnetic resonance imaging (MRI). The relaxation rate (r1 value) of PDA@MnO₂-PEG in pH=7.4 was measured to be 0.310 mM-1·S-1, while that in pH=6 became 4.364 mM-1·S-1. In mice tumor models, MRI of tumors exhibited dramatically whitening effects compared with the signal before injection. Besides, the in vivo experiments revealed that the tumors in PTT group with PDA@MnO₂-PEG injection and NIR laser irradiation were almost eliminated within 14 days, indicating the effective photothermal therapy of tumor generated by the PDA core. In conclusion, we successfully synthesized amorphous MnO₂ coated PDA core-shell nanoparticles with the function of acid-sensitive magnetic resonance imaging guided photothermal therapy, which provide a new approach for improving the effect of photothermal therapy of tumors.

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

Versatile hybrid nanoplatforms for treating periodontitis with chemical/photothermal therapy and reactive oxygen species scavenging

Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy