The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furtherm...

Nanotechnology for Multimodal Synergistic Cancer Therapy

Localized surface plasmon resonance (LSPR) in semiconductor nanocrystals (NCs) that results in resonant absorption, scattering, and near field enhancement around the NC can be tuned across a wide optical spectral range from visible to far-infrared by synthetically varying doping level, and post synthetically via chemical oxidation and reduction, photochemical control, and electrochemical control In this review, we will discuss the fundamental electromagnetic dynamics governing light matter interaction in plasmonic semiconductor NCs and the realization of various distinctive physical properties made possible by the advancement of colloidal synthesis routes to such NCs Here, we will illustrate how free carrier dielectric properties are induced in various semiconductor materials including metal oxides, metal chalcogenides, metal nitrides, silicon, and other materials We will highlight the applicability and limitations of the Drude model as applied to semiconductors considering the complex band structures 

Localized Surface Plasmon Resonance in Semiconductor Nanocrystals

Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages. With the development in nanotechnology, there have been great interests in using nanomedicine strategies to enhance radiation responses of tumors. Nanomaterials containing high-Z elements to absorb radiation rays (e.g. X-ray) can act as radio-sensitizers to deposit radiation energy within tumors and promote treatment efficacy. Nanoscale carriers are able to deliver therapeutic radioisotopes into tumors for internal RIT, or chemotherapeutic drugs for synergistically combined chemo-radiotherapy. As uncovered in recent studies, the tumor microenvironment could be modulated by various nanomedicine approaches to overcome hypoxia-associated radiation resistance. Herein, the authors will summarize the applications of nanomedicine for RT cancer treatment, and pay particular attention to the latest development of 'advanced materials' for enhanced cancer RT.

Emerging Nanotechnology and Advanced Materials for Cancer Radiation Therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) has attracted increasing attention owing to its abilities to overcome critical limitations including low tissue-penetration depth and phototoxicity in photodynamic therapy. Herein, the design of a new type of sonosensitizer is revealed, namely, ultrasmall oxygen-deficient bimetallic oxide MnWOX nanoparticles, for multimodal imaging-guided enhanced SDT against cancer. As-made MnWOX nanoparticles with poly(ethylene glycol) (PEG) modification show high physiological stability and biocompatibility. Interestingly, such MnWOX -PEG nanoparticles exhibit highly efficient US-triggered production of 1 O2 and •OH, higher than that of previously reported sonosensitizers (e.g., protoporphyrin IX and titanium dioxide), because the oxygen-deficient structure of MnWOX serves as an electron trap site to prevent electron-hole recombination. The glutathione depletion capability of MnWOX -PEG can also further favor SDT-triggered cancer cell killing. With efficient tumor homing as illustrated by computer tomography and magnetic resonance imaging, MnWOX -PEG enables effective destruction of mouse tumors under US stimulation. After accomplishing its therapeutic functions, MnWOX -PEG can be metabolized by the mouse body without any long-term toxicity. Herein, a new type of sono-sensitizing agent with high SDT efficacy, multimodal imaging functions, and rapid clearance is presented, an agent which is promising for noninvasive SDT cancer treatment.

Ultrasmall Oxygen-Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy.

Ultrasmall PEGylated Cu2-x Se nanoparticles with strong near-infrared absorption have been prepared by an ambient aqueous method. The resultant water-soluble and biocompatible nanoparticles are demonstrated to be a novel nanotheranostic agent for effective deep-tissue photoacoustic imaging, computed tomography imaging, single-photon emission computed tomography imaging, and photothermal therapy of cancer.

Ambient Aqueous Synthesis of Ultrasmall PEGylated Cu2−xSe Nanoparticles as a Multifunctional Theranostic Agent for Multimodal Imaging Guided Photothermal Therapy of Cancer

Ultrasmall biocompatible WO3 - x nanodots with an outstanding X-ray radiation sensitization effect are prepared, and demonstrated to be applicable for multi-modality tumor imaging through computed tomography and photoacoustic imaging (PAI), and effective cancer treatment combining both photothermal therapy and radiation therapy.

Shimin Zheng

Papers

Ultrasmall Biocompatible WO3- x Nanodots for Multi-Modality Imaging and Combined Therapy of Cancers.