Qing You

Indocyanine Green-Loaded Silver Nanoparticle@Polyaniline Core/Shell Theranostic Nanocomposites for Photoacoustic/Near-Infrared Fluorescence Imaging-Guided and Single-Light-Triggered Photothermal and Photodynamic Therapy

Photoacoustic (PA)/near-infrared fluorescence (NIRF) dual-modal imaging-guided phototherapy has been wide explored very recently. However, the development of high-efficiency and simplified-performed theranostic system for amplifying imaging-guided photothermal therapy/photodynamic therapy (PTT/PDT) is still a great challenge. Herein, a single-light-triggered indocyanine green (ICG)-loaded PEGylation silver nanoparticle core/polyaniline shell (Ag@PANI) nanocomposites (ICG-Ag@PANI) for PA/NIRF imaging-guided enhanced PTT/PDT synergistic effect has been successfully constructed. In this study, the synthesized Ag@PANI nanocomposites are utilized not only as the promising photothermal agent but also as potential nanovehicles for loading photosensitizer ICG via π-π stacking and hydrophobic interaction. The as-prepared ICG-Ag@PANI possesses many superior properties such as strong optical absorption in the near-infrared (NIR) region, enhanced photostability of ICG, as well as outstanding NIR laser-induced local hyperthermia and reactive oxygen species (ROS) generation. In the in vivo study, PA/NIRF dual-modal imaging confirms the accumulation and distribution of ICG-Ag@PANI in the tumor region via enhanced permeability and retention (EPR) effect. Moreover, the PTT effect of ICG-Ag@PANI rapidly raised the tumor temperature to 56.8 °C within 5 min. It is also demonstrated that the cytotoxic ROS generation ability of ICG is well maintained after being loaded onto Ag@PANI nanocomposites. Remarkably, in comparison with PTT or PDT alone, the single 808 nm NIR laser-triggered combined PTT/PDT therapy exhibits enhanced HeLa cells lethality in vitro and tumor growth inhibition in vivo.

Photosensitizer loaded PEG-MoS2–Au hybrids for CT/NIRF imaging-guided stepwise photothermal and photodynamic therapy

In this study, we developed X-ray computed tomography (CT)/near-infrared fluorescence (NIRF) imaging for visually guiding the photothermal therapy (PTT)/photodynamic therapy (PDT) of antitumor nanocomposites (PEG-MoS2-Au-Ce6), by adsorbing chlorin e6 (Ce6) to the gold nanoparticle (AuNPs)-decorated molybdenum disulfide (PEG-MoS2) nanosheets. The NIR photosensitizer Ce6 was adsorbed onto the PEG-MoS2-Au hybrids viaπ-π stacking and hydrophobic interactions, where Ce6 remained in its quenched state due to the surface plasmon resonance (SPR) capacity of AuNPs, as well as the coupling interaction with PEG-MoS2 nanosheets. However, Ce6 was dequenched and boosted strong NIR fluorescence signals after being released from the surface of PEG-MoS2-Au hybrids upon heat generation, thus producing the PDT effect for anti-tumor therapy. Moreover, the PEG-MoS2 nanosheets and Ce6 in the PEG-MoS2-Au-Ce6 nanocomposites could be further used for CT and NIRF dual-modal imaging, respectively. In vitro NIR-triggered drug release studies indicated that the PEG-MoS2-Au-Ce6 nanocomposites rapidly release the drug around the tumor site under the photothermal effect. Therefore, this dual-modality nanosystem simultaneously enables precise cancer diagnosis and therapy.

All-in-One Theranostic Nanoplatform Based on Hollow MoSx for Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy

Photodynamic therapy (PDT) kills cancer cells by converting tumor-dissolved oxygen into reactive singlet oxygen (1O2) using a photosensitizer under laser irradiation. However, pre-existing hypoxia in tumors and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers PDT efficacy. Herein, an O2 self-sufficient nanotheranostic platform based on hollow MoSx nanoparticles (HMoSx) with oxygen-saturated perfluorohexane (O2@PFH) and surface-modified human serum albumin (HSA)/chloride aluminium phthalocyanine (AlPc) (O2@PFH@HMoSx-HSA/AlPc), has been designed for the imaging and oxygen self-enriched photodynamic therapy (Oxy-PDT) of cancer. Methods: The in vitro anti-cancer activity and intracellular 1O2 generation performance of the nanoparticles were examined using 4T1 cells. We also evaluated the multimodal imaging capabilities and anti-tumor efficiency of the prepared nanoparticles in vivo using a 4T1 tumor-bearing nude mouse model. Results: This nanoplatform could achieve the distinct in vivo fluorescence (FL)/photoacoustic (PA)/X-ray computed tomography (CT) triple-model imaging-guided photothermally-maneuvered Oxy-PDT. Interestingly, the fluorescence and Oxy-PDT properties of O2@PFH@HMoSx-HSA/AlPc were considerably quenched; however, photothermal activation by 670 nm laser irradiation induced a significant increase in temperature, which empowered the Oxy-PDT effect of the nanoparticles. In this study, O2@PFH@HMoSx-HSA/AlPc demonstrated a great potential to image and treat tumors both in vitro and in vivo, showing complete tumor-inhibition over 16 days after treatment in the 4T1 tumor model. Conclusion: O2@PFH@HMoSx-HSA/AlPc is promising to be used as novel multifunctional theranostic nanoagent for triple-modal imaging as well as single wavelength NIR laser triggered PTT/Oxy-PDT synergistic therapy.

Theranostic Nanoplatform: Triple-Modal Imaging-Guided Synergistic Cancer Therapy Based on Liposome-Conjugated Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles (MSNs) have long since been investigated to provide a versatile drug-delivery platform due to their multitudinous merits. Presently, gadolinium (Gd), a T1 magnetic resonance imaging (MRI) contrast agent, was doped into MSNs as a newly emerging theranostic nanocomposite, which has received much research attention. However, it is still concerned about the dispersibility and drug leakage of MSNs. Hence, in this project, we constructed an near-infrared (NIR) irradiation-triggered, triple-modal imaging-guided nanoplatform based on doxorubicin (DOX)@Gd-doped MSNs, conjugating with indocyanine green (ICG)-loaded thermosensitive liposomes (designated as DOX@GdMSNs-ICG-TSLs). In this platform, ICG could contribute to both photodynamic therapy and photothermal therapy effects; meanwhile, it could also give play to near-infrared fluorescence imaging (NIRFI) as well as photoacoustic imaging (PAI). Consequently, NIRFI and PAI from ICG combined with the MRI function of Gd, devoted to triple-modal imaging with success. At the same time, folic acid-modified thermosensitive liposomes were explored to be coated onto the surface of DOX@GdMSNs, to solve the DOX leakage as well as improve cellular uptake. Under NIR irradiation, ICG could generate heat, thus leading to the rupture of ICG-TSLs and the release of DOX. Accordingly, the multifunctional nanocomposite appeared to be a promising meritorious theranostic nanoplatform to pave a way for treating cancer.

Magnetically-targeted and near infrared fluorescence/magnetic resonance/photoacoustic imaging-guided combinational anti-tumor phototherapy based on polydopamine-capped magnetic Prussian blue nanoparticles

In recent years, Prussian blue (PB)-based nanoagents have become a new platform in photothermal cancer treatment. However, there is little research for PB-based nanoagents to achieve synergistic phototherapy guided by multimodal imaging diagnosis and monitoring. Herein, a novel single wavelength near infrared (NIR) laser-induced magnetically targeted theranostic nanoplatform has been successfully designed and synthesized for the first time based on polydopamine (PDA)/aluminum phthalocyanine (AlPc)/bovine serum albumin (BSA) coated magnetic Prussian blue nanoparticles (Fe3O4@PB NPs) for multiple imaging-guided combinatorial cancer therapy. The resultant multifunctional Fe3O4@PB@PDA/AlPc/BSA nanocomposites show excellent stability and superparamagnetism, facilitating them to achieve superior photothermal therapy in physiological environments under magnetic guidance. In addition, the delivery vehicles can remarkably increase tumor accumulation of AlPc, thus leading to an enhanced photodynamic therapy efficacy. Furthermore, Fe3O4@PB@PDA/AlPc/BSA can be utilized as a multimodality nanoprobe for simultaneous diversified imaging, including near-infrared fluorescence imaging (NIRFI), magnetic resonance imaging (MRI), and photoacoustic imaging (PAI). Most importantly, without noticeable dark toxicity, the obtained Fe3O4@PB@PDA/AlPc/BSA nanocomposites are able to significantly suppress tumor growth via combined photothermal and photodynamic therapies upon a single 660 nm laser irradiation, achieving a superior synergetic manner compared to monotherapy both in vitro and in vivo. Therefore, our strategy provides Fe3O4@PB@PDA/AlPc/BSA nanocomposites for trimodality cancer imaging-guided synergistic therapy, with a great potential for new generation theranostics nanoagents.

Hollow Au-Cu Nanocomposite for Real-Time Tracing Photothermal/Antiangiogenic Therapy

High absorption in the near-infrared (NIR) region is essential for a photoabsorbing agents to realize efficient photothermal therapy (PTT) for cancer. Here, a novel hollow Au-Cu nanocomposite (HGCNs) is developed, which displays a significantly enhanced NIR surface plasmon resonance absorption and photothermal transduction efficiency. Besides, fluorescent polymer dots poly(9,9-dioctylfluorene-2,7-diyl-co-benzothiadiazole) (PFBT) and chemotherapeutic mammalian target of rapamycin (mTOR) inhibitor agent rapamycin (RAPA) are attached onto the HGCNs (RAPA/PFBT-HGCNs) for real-time NIR fluorescence tracing and combined PTT/antiangiogenesis therapy. In particular, due to the fluorescence resonance energy transfer effect, RAPA/PFBT-HGCNs can act as NIR-activatable on/off probe system for real-time tracing of tumor tissues. A standard in vitro cellular uptake study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dual-staining study, and flow cytometry assay reveal that the RAPA/PFBT-HGCNs combined with NIR laser exhibit higher drug accumulation and cytotoxicity in both tumor cells and epithelial cells. Moreover, the margins of tumor and normal tissue can be accurately indicated by NIR-stimulated dequenched PFBT after 24 h intravenous administration. Further, tumor growth can be considerably hampered by the optimal formulation plus laser treatment with relatively lower side effects. Consequently, the work highlights the real-time tracing and enhanced PTT/antiangiogenesis therapy prospects of the established HGCNs with tremendous potential for treatment of cancer.

CHAPTER 2:Image-guided Drug Delivery Systems Based on NIR-absorbing Nanocarriers for Photothermal-chemotherapy of Cancer

In recent years, great efforts have been given to researching multifunctional nanoagents that combine diagnostic and therapeutic functions for highly efficient and low toxicity antitumor treatments. In particular, combining real-time imaging with spatially precise photothermal therapy mediated by nanoparticles responsive to near-infrared (NIR, λ = 700–1100 nm) light through conversion of photo energy into heat has attracted interest due to its simplicity, safety and noninvasiveness, as well as targeting and remote-control properties. Apart from being directly utilized for image guided photothermal ablation of cancer, the photothermal effect of NIR-absorbing organic nanomaterials has also been exploited for remotely controlled drug release. This photothermal-controlled drug delivery system provides promising approaches to reverse multidrug resistance, for which the poor cellular uptake and insufficient intracellular drug release remain the rate-limiting steps for reaching the drug concentration level within the therapeutic window. In this chapter, we will systematically discuss the latest progress in the development of organic and inorganic nanocarriers used as a photothermal-controlled drug delivery system for the combined photo-chemotherapy of cancer. Various types of NIR-absorbing nanocarriers developed for the delivery of drugs, as well as image-guided combined photothermal-chemotherapies, will be reviewed. The final section will address the future prospects and challenges in this rapidly growing field.

One-Pot Synthesis of a Bismuth Selenide Hexagon Nanodish Complex for Multimodal Imaging-Guided Combined Antitumor Phototherapy

For integrating therapy and diagnosis into a single nanoparticle for higher antitumor efficiency and lower toxicity, our group designed a smart theranostic nanoplatform based on a hyaluronic acid-doped polypyrrole-coated bismuth selenide loading with a zinc phthalocyanine nanodish complex (Bi2Se3@HA-doped PPy/ZnPc) for multimodal imaging-guided combined phototherapy. Moreover, we expect that the HA-doped PPy smart shell for the surface functionalization will also be applied to a variety of 2D nanomaterials sharing a similar structure with Bi2Se3 to broaden their applications in biomedicine. The Bi2Se3 hexagon nanodish was synthesized via a simple and safe solution-based method compared to the commonly adopted ones. A one-pot synthesis of the naoncomplex was carried out by adding HA during the polypyrrole coating on the Bi2Se3 process, and then it was further loaded with ZnPc. Besides the good ability for infrared thermal, photoacoustic, fluorescence, and X-ray computed tomography imaging, the nanodish complex has its own high photoheat conversion efficiency for photothermal therapy, and it has remarkable optical absorption of the coefficient for photodynamic therapy. With the EPR effect of nanoparticles and the CD44-targeted effect of HA, the tumor-growth inhibition ratio of Bi2Se3@HA-doped PPy/ZnPc for PTT/PDT was as high as 96.4%, compared with that of the PTT (68.0%) or PDT (24.3%) alone, showing an excellent combined therapeutic effect. Moreover, no obvious toxicity in vivo was caused by the nanoparticles. Thus, such a Bi2Se3@HA-doped PPy/ZnPc nanodish complex has promise for real-time monitoring and precise, high-efficiency antitumor treatment.

NIRF/PA/CT multi-modality imaging guided combined photothermal and photodynamic therapy based on tumor microenvironment-responsive nanocomposites

In this study, we developed a novel chitosan (CS)-controlled and aluminum phthalocyanine chloride (AlPc)-loaded molybdenum disulfide (MoS2) nanocomposite as a single nanoplatform (AlPc-MoS2@SiO2-CS) for near-infrared fluorescence (NIRF), photoacoustic (PA), and X-ray computed tomography (CT) multi-modality imaging-guided photothermal and photodynamic combination therapy of tumors. The MoS2 nanodot was used as the PA/CT contrast as well as hyperthermal agent. The MoS2@SiO2 nanoparticles prepared by a facile one-pot approach can serve as drug-delivery vehicles to transport the NIR absorbing photosensitizer AlPc within the mesoporous cavities. Meanwhile, a natural cationic polysaccharide, CS, was introduced as a gatekeeper to avoid the premature release of loaded AlPc. Whats more, CS as a tumor microenvironment-responsive agent can control the release of loaded drugs to the acidic local environment in the tumor. The in vivo multimodal imaging uncovered that the AlPc-MoS2@SiO2-CS nanocomposites showed enhanced tumor uptake and diagnosis abilities after intravenous injection. More importantly, the nanocomposites exhibited an evident near-infrared induced photothermal effect in the in vitro and in vivo experiments, which remarkably improved the photodynamic therapy efficiency by accelerating the blood flow and subsequently increasing oxygen supply in the tumor. Taken together, our current work demonstrated a nanoplatform for multimodal imaging guided targeted dual-therapy, which revealed a potential strategy for tumor treatment.