Gold nanoechinus can sensitize the formation of singlet oxygen in the first and the second near-infra red (NIR) biological windows and exert in vivo dual modal photodynamic and photothermal therapeutic effects (PDT and PTT) to destruct the tumors completely. This is the first literature example of the destruction of tumors in NIR window II induced by dual modal nanomaterial-mediated photodynamic and photothermal therapy (NmPDT & NmPTT).

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Therapeutic efficacy of glioblastoma multiforme (GBM) is often severely limited by poor penetration of therapeutics through blood-brain barrier (BBB) into brain tissues and lack of tumor targeting. In this regard, a functionalized upconversion nanoparticle (UCNP)-based delivery system which can target brain tumor and convert deep tissue-penetrating near-infrared (NIR) light into visible light for precise phototherapies on brain tumor was developed in this work.Methods: The UCNP-based phototherapy delivery system was acquired by assembly of oleic acid-coated UCNPs with angiopep-2/cholesterol-conjugated poly(ethylene glycol) and the hydrophobic photosensitizers. The hybrid nanoparticles (ANG-IMNPs) were characterized by DLS, TEM, UV/vis and fluorescence spectrophotometer. Cellular uptake was examined by laser scanning confocal microscopy and flow cytometry. The PDT/PTT effect of ANG-IMNPs was evaluated using MTT assay. Tumor accumulation of NPs was determined by a non-invasive in vivo imaging system (IVIS). The in vivo anti-glioma effect of ANG-IMNPs was evaluated by immunohistochemical (IHC) examination of tumor tissues and Kaplan-Meier survival analysis.Results: In vitro data demonstrated enhanced uptake of ANG-IMNPs by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered PDT and PTT. In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro, the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC tissue examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days).Conclusion: In vitro and in vivo data strongly indicate that the ANG-IMNPs were capable of selectively delivering dual photosensitizers to brain astrocytoma tumors for effective PDT/PTT in conjugation with a substantially improved median survival. The therapeutic efficacy of ANG-IMNPs demonstrated in this study suggests their potential in overcoming BBB and establishing an effective treatment against GBM.

Singlet oxygen ( 1 O 2 ) is known to play an indispensible role in the photodynamic therapy (PDT) treatment of cancer, [1][2][3][4][5] and is an important oxidant for hydroperoxidation of olefins in organic synthesis. [6,7] Singlet O 2 is conventionally formed by sensitization by organic photosensitizers, such as Rose Bengal, silicon phthalocyanine, etc. [1][2][3][4][5][6][7] These organic or organometallic dyes are, however, prone to photoinduced degradation and enzymatic degradation, which becomes problematic in PDT treatments, and reduces the efficiency of the generation of singlet O 2 . [5,8] It is, therefore, important to search for photosensitizers with highly efficient singlet O 2 generation and large absorption coefficients that are photochemically more stable and less prone to enzymatic degradation.Previously, it was reported that the yield of singlet oxygen production by a photosensitizer, namely, Rose Bengal, was enhanced by a silver island film through the metal-enhanced absorption of photosensitizer. [9,10] It was also reported that a gold nanodisk could enhance the phosphorescence decay rate of singlet oxygen, leading to a larger characteristic phosphorescence emission band of singlet oxygen at 1270 nm. [11] In another two studies, it was observed that the quantum yield of singlet O 2 formation generated by phthalocyanine photosensitizers can be enhanced by the presence of gold nanoparticles. [12,13] Herein we report an unprecedented observation that singlet oxygen can be formed through direct sensitization by metal nanoparticles (M NPs, M = Ag, Pt, and Au) without the presence of any organic photosensitizers. Unambiguous experimental evidence includes direct observation of singlet oxygen emission at roughly 1268 nm, hydroperoxidation of cyclohexene, green fluorescence from a selective singlet oxygen fluorescent sensor, namely, Singlet Oxygen Sensor Green (SOSG, Molecular Probe), and quenching of singlet oxygen phosphorescence by sodium azide.As shown in Figure 1, photoexcitation of M NPs at the surface plasmon resonance absorption bands of Ag (d = 55, 42 nm), Pt (10 nm), and Au (22 nm) in D 2 O results in characteristic singlet oxygen emission at 1264 and 1268 nm, respectively. Control experiments show that in the absence of metal nanoparticles, photoexcitation of poly(vinyl pyrrolidone (PVP) in D 2 O using either 254 or 508 nm light did not result in any detectable singlet O 2 emission signal (see the Figure 1. a) Phosphorescence emission spectra of singlet oxygen sensitized by Au, Ag or Pt nanoparticles in D 2 O, and a control experiment with PVP in D 2 O in the absence of metal nanoparticles (purple line, l ex = 254 nm and blue line, l ex = 508 nm). b) The extinction spectra (solid lines) of Ag, Pt, and Au NPs, and the excitation spectra (dashed lines) of singlet O 2 phosphorescence at 1270 nm in the presence of Ag, Pt, and Au NPs, respectively. A longpass filter of 850 nm was put between the sample and the detector for all experiments (unless otherwise mentioned) to filter away any stray light ...

High-yield multibranched Au nanoechinus possessing lengthy and dense branched nanorods on the surface were synthesized using a seed-mediated surfactant-directed approach in the presence of gemini cationic surfactant N,N,N'N'-tetramethyl-N,N'-ditetradecylethane-1,2-diaminium bromide (C14C2C14Br2), HAuCl4, AgNO3, and ascorbic acid. C14C2C14Br2 surfactant provides a versatile template in designing the unique morphology of Au nanoechinus with the assistance of AgNO3. UV-vis spectroscopic analysis proves that Au nanoechinus possess a unique intense broad localized surface plasmon resonance (LSPR) peak, which extends from 400 to 1700 nm in the NIR region making a highly potential platform for biomedical applications. Systematic time-dependent TEM, UV-vis-NIR, and XRD analysis were performed to monitor the morphological evolution of multibranched Au nanoechinus. It was found that the surface of branched nanorods of Au NE preferentially grew along (111) crystal planes. Furthermore, as-synthesized Au nanoechinus shows excellent SERS enhancement ability for dopamine inside HeLa cells.