Surface-enhanced Raman scattering from Au nanorods, nanotriangles, and nanostars with tuned plasmon resonances.

Electromagnetic theory predicts that the optimal value of the localized plasmon resonance (LPR) wavelength for the maximal SERS enhancement factor (EF) is half the sum of the laser and Raman wavelengths. For small Raman shifts, the theoretical EF scales as the fourth power of the local field. However, experimental data often disagree with these theoretical conclusions, leaving the question of choosing the optimal plasmon resonance for the maximal SERS signal unresolved. Here, we present experimental data for gold nanorods (AuNRs), gold nanotriangles (AuNTs), and gold nanostars (AuNSTs) simulating 1D, 2D, and 3D plasmonic nanostructures, respectively. The LPR wavelengths were tuned by chemical etching within 580-1020 nm at a constant concentration of the particles. The particles were functionalized with Cy7.5 and NBT, and the dependence of the intensity at 940 cm-1 (Cy7.5) and 1343 cm-1 (NBT) on the LPR wavelength was examined for laser wavelengths of 633 nm and 785 nm. The electromagnetic SERS EFs were calculated by averaging the product of the local field intensities at the laser and Raman wavelengths over the particle surface and their random orientations. The calculated SERS plasmonic profiles were redshifted compared to the laser wavelength. For 785 nm excitation, the calculated EFs were five to seven times higher than those for 633 nm excitation. With AuNR@Cy7.5 and AuNT@ Cy7.5, the experimental SERS was 35-fold stronger than it was with NBT-functionalized particles, but with AuNST@Cy7.5 and AuNST@NBT, the SERS responses were similar. With all nanoparticles tested, the SERS plasmonic profiles after 785 nm excitation were slightly blue-shifted, as compared with the laser wavelength, possibly owing to the inner filter effect. After 633 nm excitation, the SERS profiles were red-shifted, in agreement with EM theory. In all cases, the plasmonic EF profiles were much broadened compared to the calculated ones and did not follow the four-power law.

Resonant Concentration-Driven Control of Dye Molecule Photodegradation via Strong Optical Coupling to Plasmonic Nanoparticles.

Photobleaching is one of the basic chemical processes that occur naturally in organic molecules. In this work, we investigate the quantum dynamics of Cy 7.5 dye molecules optically coupled to Au nanorod particles and experimentally demonstrate the decrease of the photobleaching rate in this hybrid system. We discover the effect of a resonance-like behavior not observed before for any type of emitter─the photobleaching rate of the dye molecules reaches a minimum for a suitable number of molecules coupled to the nanoparticle. The manifestation of the effect is the consequence of shifts in the energy levels in the hybrid system caused by the change in the number of molecules coupled to a nanoparticle. The energy shifts are the prerequisite for the effective depopulation of the triplet level, which is responsible for the photodegradation mechanism. The discovered effect paves the way for increasing the efficiency of optoelectronic and photovoltaic devices.

Design of an Artificial Opal/Photonic Crystal Interface for Alcohol Intoxication Assessment: Capillary Condensation in Pores and Photonic Materials Work Together.

Alcohol intoxication has a dangerous effect on human health and is often associated with a risk of catastrophic injuries and alcohol-related crimes. A demand to address this problem adheres to the design of new sensor systems for the real-time monitoring of exhaled breath. We introduce a new sensor system based on a porous hydrophilic layer of submicron silica particles (SiO2 SMPs) placed on a one-dimensional photonic crystal made of Ta2O5/SiO2 dielectric layers whose operation relies on detecting changes in the position of surface wave resonance during capillary condensation in pores. To make the active layer of SiO2 SMPs, we examine the influence of electrostatic interactions of media, particles, and the surface of the crystal influenced by buoyancy, gravity force, and Stokes drag force in the frame of the dip-coating preparation method. We evaluate the sensing performance toward biomarkers such as acetone, ammonia, ethanol, and isopropanol and test sensor system capabilities for alcohol intoxication assessment. We have found this sensor to respond to all tested analytes in a broad range of concentrations. By processing the sensor signals by principal component analysis, we selectively determined the analytes. We demonstrated the excellent performance of our device for alcohol intoxication assessment in real-time.

SERS and Indicator Paper Sensing of Hydrogen Peroxide Using Au@Ag Nanorods.

The detection of hydrogen peroxide and the control of its concentration are important tasks in the biological and chemical sciences. In this paper, we developed a simple and quantitative method for the non-enzymatic detection of H2O2 based on the selective etching of Au@Ag nanorods with embedded Raman active molecules. The transfer of electrons between silver atoms and hydrogen peroxide enhances the oxidation reaction, and the Ag shell around the Au nanorod gradually dissolves. This leads to a change in the color of the nanoparticle colloid, a shift in LSPR, and a decrease in the SERS response from molecules embedded between the Au core and Ag shell. In our study, we compared the sensitivity of these readouts for nanoparticles with different Ag shell morphology. We found that triangle core-shell nanoparticles exhibited the highest sensitivity, with a detection limit of 10-4 M, and the SERS detection range of 1 × 10-4 to 2 × 10-2 M. In addition, a colorimetric strategy was applied to fabricate a simple indicator paper sensor for fast detection of hydrogen peroxide in liquids. In this case, the concentration of hydrogen peroxide was qualitatively determined by the change in the color of the nanoparticles deposited on the nitrocellulose membrane.

Petal-like Gap-Enhanced Raman Tags with Controllable Structures for High-Speed Raman Imaging.

Surface-enhanced Raman scattering (SERS) is widely used for in vitro and in vivo bioimaging applications. However, reproducible and controllable fabrication of SERS tags with high density of electromagnetic hot-spots is still challenging. We report an improved strategy for the synthesis of core/shell Raman tags with high density of hot-spots and high immobilization of reporter molecules. The strategy is based on simultaneous growth and functionalization of an Au shell around Au nanospheres coated with 4-nitrobenzenethiol (NBT). The amount of added 4-NBT is key factor to control the structure SERS response of the resulting particles. Specifically, we demonstrate the formation of gap-enhanced Raman tags (GERTs) with a smooth solid shell (sGERTs), petal-like GERTs (pGERTs), and mesoporous Au particles (mGERTs) filled with Raman molecules. In contrast to NBT molecules, similar thiols such as 1,4-benzenedithiol (BDT) and 2-naphtalenethiol (NT) do not support the formation of pGERTs and mGERTs. To explain this finding, we proposed a growth mechanism based on the unique chemical structure of NBT. The SERS response of optimized pGERTs is 50 times higher than that from usual sGERTs, which makes pGERTs suitable for single-particle spectroscopy. We demonstrate successful application of pGERTs for high-speed cell imaging using 10 ms accumulation time per pixel and a total imaging time of about 1 min. Because of the high SERS response and unique porous structure, these nanoparticles have great potential for bioimaging and other applications.

Advantages of Highly Spherical Gold Nanoparticles as Labels for Lateral Flow Immunoassay.

The use of lateral flow immunoassays (LFIAs) for rapid on-site testing is restricted by their relatively high limit of detection (LoD). One possible way to decrease the LoD is to optimize nanoparticle properties that are used as labels. We compare two types of Au nanoparticles: usual quasispherical gold nanoparticles (C-GNPs), obtained by the Turkevich-Frens method, and superspherical gold nanoparticles (S-GNPs), obtained by a progressive overgrowth technique. Average diameters were 18.6-47.5 nm for C-GNPs and 20.2-90.4 nm for S-GNPs. Cardiomarker troponin I was considered as the target analyte. Adsorption and covalent conjugation with antibodies were tested for both GNP types. For C-GNPs, the minimal LoD was obtained with 33.7 nm nanoparticles, reaching 12.7 ng/mL for covalent immobilization and 9.9 ng/mL for adsorption. The average diameter of S-GNPs varied from 20.2 to 64.5 nm, which resulted in a decrease in LoD for an LFIA of troponin I from 3.4 to 1.2 ng/mL for covalent immobilization and from 2.9 to 2.0 ng/mL for adsorption. Thus, we obtained an 8-fold decrease in LoD (9.9 to 1.2 ng/mL) by using S-GNPs. This effect can be related to more effective antibody immobilization and improved S-GNP optical properties. The obtained results can improve LFIAs for various practically significant analytes.

Carbon dot aggregates as an alternative to gold nanoparticles for the laser-induced opening of microchamber arrays.

Carbon dots (CDs) are usually used as an alternative to other fluorescent nanoparticles. Apart from fluorescence, CDs also have other important properties for use in composite materials, first of all their ability to absorb light energy and convert it into heat. In our work, for the first time, CDs have been proposed as an alternative to gold nanostructures for harvesting light energy, which results in the opening of polymer-based containers with biologically active compounds. In this paper, we propose a method for the synthesis of polylactic acid microchamber arrays with embedded CDs. A comparative analysis was made of the damage to microchambers functionalized with gold nanorods and with CD aggregates, depending on the wavelength and power of the laser used. The release of fluorescent cargo from the microchamber arrays with CD aggregates under laser exposure was demonstrated.

Plasmonic photothermal therapy: Approaches to advanced strategy.

BACKGROUND: The analysis of recent studies on plasmonic photothermal therapy (PPT) after intravenous administration of gold nanorods (GNRs) has demonstrated that the effectiveness of nanoparticle-assisted laser hyperthermia depends on a correct dosage strategy of nanoparticle administration. Accumulation of GNRs in tumor tissue dramatically increases the local heating of the tumor without damage to healthy tissues. However, the optimal doses of GNR intravenous injections (IVIs) for effective accumulation in tumors, and optimal protocols of PPT are not designed yet. The current study aims to improve the efficacy of PPT in tumor-bearing rats using multiple fractional intravenous administration of GNRs. MATERIALS AND METHODS: For PPT experiments, the GNRs with aspect ratio of 4.1 were functionalized with thiolated polyethylene glycol (PEG) and their suspensions were used for multiple fractional intravenous administration in outbred albino male rats with experimental model of rat liver cancer (cholangiocarcinoma line PC-1). Doppler ultrasonography was performed to characterize the vascularity of transplanted rat tumors before any treatment. After a final injection of GNRs, tumor was irradiated during 15 minutes by 808-nm NIR diode laser at a power density 2.3 W/cm2 . The animals were withdrawn from the experiment and sampling of tissues for morphological study and gold accumulation was performed 24 hours and 3 weeks after PPT. RESULTS: The multiple IVIs of gold nanorods and further PPT of transplanted cholangiocarcinoma provided significant damage to tumor tissue resulting in pronounced necrotic mass and retardation of the tumor growth. More importantly, the proposed PPT protocol had low toxicity as evidenced by histological examination of internal organs. The efficiency of PPT depends on the presence of newly formed vasculature as revealed by the Doppler ultrasound investigation. CONCLUSION: The repeatable IVIs promote greater of GNR accumulation within the tumor thus resulting in higher PPT efficacy. Accompanying ultrasonography can be useful for prognosis and monitoring of treatment. Lasers Surg. Med. 50:1025-1033, 2018. © 2018 Wiley Periodicals, Inc.

Gold Nanorod Mediated Chlorhexidine Microparticle Formation and Near-Infrared Light Induced Release.

Gold nanorods (GNR) are good light harvesting species for elaboration of near-infrared (NIR) responsive drug delivery systems. Herein, chlorhexidine microparticles are grown directly on the surface of gold nanorods and then stabilized with polyelectrolyte multilayer encapsulation, producing novel composite drug-GNR particles with high drug loading and NIR light sensitivity. Crystallization of chlorhexidine is caused by the ionic strength of the chloride solution that has been demonstrated via formation of a homogeneous porous spherical structure at 0.33 M CaCl2. By introducing GNRs into the CaCl2 solution, the nucleation of chlorhexidine molecules and size of produced spheres are affected, since GNRs act as sites for chlorhexidine nucleation. Similarly, when GNRs are replaced by chlorhexidine seeds (5.2 ± 1.7 µm), a core-shell crystal structure is observed. The encapsulated GNR/chlorhexidine composites are responsive to NIR light (840 nm) that increases the temperature at the chlorhexidine crystals, followed by microparticle dissolution and rupture of capsules which is illustrated with confocal microscopy and SEM. Furthermore, a stepwise burst release of chlorhexidine can be induced by multiple cycles of NIR light exposure. The GNR/chlorhexidine composites show good biocompatibility and antimicrobial activity. The proposed method of antibacterial drug release may therefore indicate that this NIR responsive chlorhexidine composite may be useful for future clinical applications.

In vitro and in vivo MRI visualization of nanocomposite biodegradable microcapsules with tunable contrast.

Microcapsules, made of biodegradable polymers, containing magnetite nanoparticles with tunable contrast in both the T1 and T2 MRI modes, were successfully prepared using a layer-by-layer approach. The MRI contrast of the microcapsules was shown to depend on the distance between magnetite nanoparticles in the polymeric layers, which is controlled by their concentration in the microcapsule shell. A fivefold increase in the average distance between the nanoparticles in the microcapsule shell led to a change in the intensity of the MR signal of 100% for both the T1 and T2 modes. Enzyme treatment of biodegradable shells resulted in a change of the microcapsules' MRI contrast. In vivo degradation of nanocomposite microcapsules concentrated in the liver after intravenous injection was demonstrated by MRI. This method can be used for the creation of a new generation of drug delivery systems, including drug depot, with combined navigation, visualization and remote activated release of bioactive substances in vivo.

Composite SERS-based satellites navigated by optical tweezers for single cell analysis.

Herein, we have designed composite SERS-active micro-satellites, which exhibit a dual role: (i) effective probes for determining cellular composition and (ii) optically movable and easily detectable markers. The satellites were synthesized by the layer-by-layer assisted decoration of silica microparticles with metal (gold or silver) nanoparticles and astralen in order to ensure satellite SERS-based microenvironment probing and satellite recognition, respectively. A combination of optical tweezers and Raman spectroscopy can be used to navigate the satellites to a certain cellular compartment and probe the intracellular composition following cellular uptake. In the future, this developed approach may serve as a tool for single cell analysis with nanometer precision due to the multilayer surface design, focusing on both extracellular and intracellular studies.

Nanoplasmonically-induced defects in lipid membrane monitored by ion current: transient nanopores versus membrane rupture.

We have developed a nanoplasmonic-based approach to induce nanometer-sized local defects in the phospholipid membranes. Here, gold nanorods and nanoparticles having plasmon resonances in the near-infrared (NIR) spectral range are used as optical absorption centers in the lipid membrane. Defects optically induced by NIR-laser irradiation of gold nanoparticles are continuously monitored by high-precision ion conductance measurement. Localized laser-mediated heating of nanorods and nanoparticle aggregates cause either (a) transient nanopores in lipid membranes or (b) irreversible rupture of the membrane. To monitor transient opening and closing, an electrophysiological setup is assembled wherein a giant liposome is spread over a micrometer hole in a glass slide forming a single bilayer of high Ohmic resistance (so-called gigaseal), while laser light is coupled in and focused on the membrane. The energy associated with the localized heating is discussed and compared with typical elastic parameters in the lipid membranes. The method presented here provides a novel methodology for better understanding of transport across artificial or natural biological membranes.

Overgrowth of gold nanorods by using a binary surfactant mixture.

Seed-mediated surfactant-assisted growth is widely used as the most effective method for gold nanorod (NR) synthesis. Using prepared nanorods as seeds for further overgrowth can increase the dimensional tunability of the final particles. However, overgrowth in usual cetyltrimethylammonium bromide (CTAB) surfactant solutions leads to poor control of the final particle shape and size. In this work, we report an improved strategy to demonstrate the controllable overgrowth of gold NRs in the binary surfactant mixture sodium oleate (NaOL) + CTAB. This approach overcomes the difficulty of growing NR suspensions with small amounts of impurities. By controlling the total amount of added NR seeds, it is possible to tune the average length, diameter, and plasmon resonances of overgrown particles in a wide range. Together with the original NaOL + CTAB method developed by Murray and co-workers ( Nano Lett. 2013 , 13 , 555 ), this overgrowth approach expands the dimensional and plasmonic tunability of the fabrication technology without any decrease in the monodispersity and purity of samples.

Large-scale high-quality 2D silica crystals: dip-drawing formation and decoration with gold nanorods and nanospheres for SERS analysis.

High-quality colloidal crystals (CCs) are important for use in photonic research and as templates for large-scale plasmonic SERS substrates. We investigated how variations in temperature, colloid concentration, and dip-drawing parameters (rate, incubation time, etc) affect the structure of 2D CCs formed by highly monodisperse silica nanoparticles (SiNPs) synthesized in an l-arginine solution and regrown by a modified Stöber method. The best quality 2D CCs were obtained with aqueous 12 wt% colloids at a temperature of 25 °C, an incubation time of 1 min, and a drawing rate of 50 mm min(-1). Assembling of gold nanorods (GNRs) on 2D CCs resulted in the formation of ring-like chains with a preferential tail-to-tail orientation along the hexagonal boundaries. To the best of our knowledge, this is the first time that such nanostructures have been prepared. Owing to the preferential tail-to-tail packing of GNRs, 2D SiNP CC + GNR substrates demonstrated an analytical SERS enhancement of about 8000, which was 10 to 15 times higher than that for self-assembled GNRs on a silicon wafer. In addition, the analytical SERS enhancement was almost 60 times lower after replacing the nanorods in 2D SiNP CC + GNR substrates with 25 nm gold nanospheres.

Extinction and extra-high depolarized light scattering spectra of gold nanorods with improved purity and dimension tunability: direct and inverse problems.

The experimental depolarized light scattering ratio IVH/IVV of plasmonic nanorods is strongly decreased by a co-polarized contribution from impurity particles inevitably presented in suspensions fabricated by common seed-mediated methods with a single surfactant [typically, hexadecyltrimethylammonium bromide (CTAB)]. We used a binary NaOL (sodium oleate) + CTAB surfactant method (Ye et al., Nano Lett., 2013, 13, 555) to dramatically decrease the percentage of impurity particles in suspensions of as-prepared and overgrown nanorods without any separation procedures. The as-prepared nanorods demonstrated a very high ratio of longitudinal to transversal plasmonic maxima (of about 7) and an unprecedented, extra-high depolarized light scattering ratio IVH/IVV (of about 60%). To the best of our knowledge, this is the first experimental demonstration of the depolarized light scattering ratio approaching the theoretical limit of 75%. The NaOL + CTAB growing solution was also used to increase the nanorod diameters and lengths by a controllable overgrowing process. Statistical TEM data for as-prepared and overgrown nanorods were used to solve a direct problem, i.e. for T-matrix simulation of the extinction and depolarized light scattering spectra. To solve an inverse problem, with the extinction peak wavelength and full width at half-maximum (FWHM) as the input parameters, we obtained calibration plots to quantify the aspect ratio distribution in terms of a simple two-parametric log-normal model. Simultaneous fitting of the T-matrix calculations of extinction and depolarized light scattering spectra to the experimental data enabled us to retrieve the aspect ratio distribution and the percentage of impurity particles, in excellent agreement with statistical estimations based on transmission electron microscopy images.

Optical detection of infectious SARS-CoV-2 virions by counting spikes.

Existing methods for the mass detection of viruses are limited to the registration of small amounts of a viral genome or specific protein markers. In spite of high sensitivity, the applied methods cannot distinguish between virulent viral particles and non-infectious viral particle debris. We report an approach to solve this long-standing challenge using the SARS-CoV-2 virus as an example. We show that wide-field optical microscopy with the state-of-the-art mesoscopic fluorescent labels, formed by a core-shell plasmonic nanoparticle with fluorescent dye molecules in the core-shell that are strongly coupled to the plasmonic nanoparticle, not only rapidly, i.e. in less than 20 minutes after sampling, detects SARS-CoV-2 virions directly in a patient sample without a pre-concentration step, but can also distinguish between infectious and non-infectious virus strains by counting the spikes on the lipid envelope of individual viral particles.

Monitoring of optical properties of tumors during laser plasmon photothermal therapy.

We studied grafted tumors obtained by subcutaneous implantation of kidney cancer cells into male white rats. Gold nanorods with a plasmon resonance of about 800 nm were injected intratumorally for photothermal heating. Experimental irradiation of tumors was carried out percutaneously using a near-infrared diode laser. Changes in the optical properties of the studied tissues in the spectral range 350-2200 nm under plasmonic photothermal therapy (PPT) were studied. Analysis of the observed changes in the absorption bands of water and hemoglobin made it possible to estimate the depth of thermal damage to the tumor. A significant decrease in absorption peaks was observed in the spectrum of the upper peripheral part and especially the tumor capsule. The obtained changes in the optical properties of tissues under laser irradiation can be used to optimize laboratory and clinical PPT procedures.

Plasmonic nanopowders for photothermal therapy of tumors.

We describe a novel strategy for the fabrication of plasmonic nanopowders (dried gold nanoparticles) by using wet chemical nanoparticle synthesis, PEG-SH functionalization, and a standard freeze-drying technique. Our strategy is illustrated by successful fabrication of different plasmonic nanopowders, including gold nanorods, gold-silver nanocages, and gold nanospheres. Importantly, the dried nanoparticles can be stored for a long time under usual conditions and then can easily be dissolved in water at a desired concentration without such hard manipulations as sonication or heating. Redispersed samples maintain the plasmonic properties of parent colloids and do not form aggregates. These properties make pegylated freeze-dried gold nanoparticles attractive candidates for plasmonic photothermal therapy in clinical settings. In this work, redispersed gold nanorods were intravenously administered to mice bearing Ehrlich carcinoma tumors at doses of 2 and 8 mg (Au)/kg (animal). Particle biodistribution was measured by atomic absorption spectroscopy, and tumor hyperthermia effects were studied under laser NIR irradiation. Significant tumor damage was observed only at the higher dose of the nanorods.

Albumin-Based Nanocarriers for the Simultaneous Delivery of Antioxidant Gene and Phytochemical to Combat Oxidative Stress.

Human serum albumin (HSA) nanoparticles are promising biocompatible, nontoxic, and non-immunogenic platforms for biomedical applications such as bioimaging and drug and gene delivery. The development of nonviral gene delivery vectors is a great challenge for efficient and safe gene therapy. Sulforaphane (SF) can stimulate the expression of antioxidant genes via activation of a nuclear transcription factor, the erythroid-2 related factor 2 (Nrf-2). Here, we use polyethyleneimine (PEI)-stabilized HSA nanoparticles to stimulate endogenous antioxidant defense mechanisms in lung epithelial cells L-132 through the combinatorial effect of SF drug and antioxidant superoxide dismutase 1 gene (pSOD1 plasmid) delivered by HSA-PEI-SF-pSOD1 nanocomposites (NCs). The developed NCs demonstrated high biocompatibility (L-132 viability, >95%, MTT assay) and high antioxidant activity because of efficient entry of the SOD1 gene and SF-loaded NCs at a very low (3 µg) dose in L-132 cells. A high transfection efficiency of L-132 cells (∼66%, fluorescent microscopy) was obtained with the GFP-tagged transgene SOD1-GFP. We speculate that the antioxidant activity of HSA-PEI-SF-pSOD1 NCs in L-132 cells is due to the initial release of SF followed by subsequent SOD1 gene expression after three to four days of incubation. Hence, the developed HSA-based NCs can be efficient biocompatible nanocarriers for safe and effective drug and gene delivery applications to treat diseases with high oxidative stress due to combinatorial SF and SOD1 gene mechanisms.

Photothermal and Photodynamic Therapy of Tumors with Plasmonic Nanoparticles: Challenges and Prospects.

Cancer remains one of the leading causes of death in the world. For a number of neoplasms, the efficiency of conventional chemo- and radiation therapies is insufficient because of drug resistance and marked toxicity. Plasmonic photothermal therapy (PPT) using local hyperthermia induced by gold nanoparticles (AuNPs) has recently been extensively explored in tumor treatment. However, despite attractive promises, the current PPT status is limited by laboratory experiments, academic papers, and only a few preclinical studies. Unfortunately, most nanoformulations still share a similar fate: great laboratory promises and fair preclinical trials. This review discusses the current challenges and prospects of plasmonic nanomedicine based on PPT and photodynamic therapy (PDT). We start with consideration of the fundamental principles underlying plasmonic properties of AuNPs to tune their plasmon resonance for the desired NIR-I, NIR-2, and SWIR optical windows. The basic principles for simulation of optical cross-sections and plasmonic heating under CW and pulsed irradiation are discussed. Then, we consider the state-of-the-art methods for wet chemical synthesis of the most popular PPPT AuNPs such as silica/gold nanoshells, Au nanostars, nanorods, and nanocages. The photothermal efficiencies of these nanoparticles are compared, and their applications to current nanomedicine are shortly discussed. In a separate section, we discuss the fabrication of gold and other nanoparticles by the pulsed laser ablation in liquid method. The second part of the review is devoted to our recent experimental results on laser-activated interaction of AuNPs with tumor and healthy tissues and current achievements of other research groups in this application area. The unresolved issues of PPT are the significant accumulation of AuNPs in the organs of the mononuclear phagocyte system, causing potential toxic effects of nanoparticles, and the possibility of tumor recurrence due to the presence of survived tumor cells. The prospective ways of solving these problems are discussed, including developing combined antitumor therapy based on combined PPT and PDT. In the conclusion section, we summarize the most urgent needs of current PPT-based nanomedicine.