Photothermal Conversion Agents Research Articles

Triggered release of antimicrobial peptide from microneedle patches for treatment of wound biofilms.

Biofilms pose a great challenge for wound management. Herein, this study describes a near-infrared (NIR) light-responsive microneedle patch for on-demand release of antimicrobial peptide for treatment of wound biofilms. IR780 iodide as a photothermal conversion agent and molecularly engineered peptide W379 as an antimicrobial agent are loaded in dissolvable poly(vinylpyrrolidone) (PVP) microneedle patches followed by coating with a phase change material 1-tetradecanol (TD). After placing in an aqueous solution or biofilm containing wounds ex vivo and in vivo, upon exposure to NIR light, the incorporated IR780 induces light-to-heat conversion, causing the melting of TD. This leads to the dissolution of PVP microneedles, enabling the release of loaded W379 peptide from the microneedles into surrounding regions (e.g., solution, biofilm, wound bed). Compared with traditional microneedle patches, NIR light responsive microneedle patches can program the release of antimicrobial peptide and show high antibacterial efficacy in vitro. Meanwhile, this work indicates that NIR light responsive TD-coated, W379-loaded PVP microneedle patches show excellent antibiofilm activities ex vivo and in vivo. Additionally, this microneedle system could be a promising platform for delivering other antimicrobial agents.

HDAC6 inhibitor loaded bimetallene nanosheets with antagonizing thermoresistance for augmented mild photothermal therapy

Photothermal therapy (PTT) induces thermoresistance through cellular heat shock response, which impairs the therapeutic efficacy of the PTT. To resolve this problem, we developed a photothermal theranostics (denoted as PMH), which integrated the photothermal conversion agent of PdMo bimetallene with histone deacetylase 6 (HDAC6) selected inhibitor (ACY-1215), showing the synergistic antitumor effect both in vitro and in vivo. Mechanistically, under the photoacoustic imaging (PA) navigation, the released ACY-1215 triggered by NIR laser irradiation decrease the heat shock proteins (HSPs) expression and weaken the HDAC6-regulated HSP90 deacetylation, thus hindering the degradation of PTT-induced misfolded or unfold proteins through proteasome dependent pathway. Moreover, mild photothermal therapy (mPTT) treatment compromised the autophagy, which induced by HDAC6 inhibition, leading to mPTT-induced misfolded or unfold proteins further accumulation. Given that inhibition of HDAC6 plus mPTT contribute to tumor eradication. This study develops a promising combination strategy based on mPTT for future cancer treatment.

BSA-templated synthesis of Ir/Gd bimetallic oxide nanotheranostics for MR/CT imaging-guided photothermal and photodynamic synergistic therapy.

Precision medicine urges the development of theranostics which can efficiently integrate precise diagnosis and effective therapy. In this study, a facile synthesis of Ir/Gd bimetallic oxide nanotheranostics (termed BSA@Gd2O3/IrO2 NPs) with good biocompatibility was demonstrated using a biomineralization method where bovine serum albumin (BSA) served as a versatile template. BSA@Gd2O3/IrO2 NPs exhibited high longitudinal relaxivity (5.2 mM-1 s-1) and X-ray absorption capability (14.5 Hu mM-1), illustrating them to be a good contrast agent for magnetic resonance (MR) and computed tomography (CT) dual-modal imaging. Moreover, BSA@Gd2O3/IrO2 NPs can act as not only a photothermal conversion agent with ultrahigh efficiency (66.7%) as well as a good photosensitizer, but also an effective catalase to decompose endogenous H2O2 to produce O2, thus relieving hypoxia and enhancing the phototherapeutic effect. Both in vitro and in vivo experiments demonstrated the high effectiveness of BSA@Gd2O3/IrO2 NPs in MR/CT dual-modal imaging and photothermal and photodynamic synergistic tumor treatments. This work sheds new light on the development of versatile nanotheranostic systems using mild and robust biomineralization methods.

Combined Photodynamic and Photothermal Therapy and Immunotherapy for Cancer Treatment: A Review.

Photoactivation therapy based on photodynamic therapy (PDT) and photothermal therapy (PTT) has been identified as a tumour ablation modality for numerous cancer indications, with photosensitisers and photothermal conversion agents playing important roles in the phototherapy process, especially in recent decades. In addition, the iteration of nanotechnology has strongly promoted the development of phototherapy in tumour treatment. PDT can increase the sensitivity of tumour cells to PTT by interfering with the tumour microenvironment, whereas the heat generated by PTT can increase blood flow, improve oxygen supply and enhance the PDT therapeutic effect. In addition, tumour cell debris generated by phototherapy can serve as tumour-associated antigens, evoking antitumor immune responses. In this review, the research progress of phototherapy, and its research effects in combination with immunotherapy on the treatment of tumours are mainly outlined, and issues that may need continued attention in the future are raised.

Novel properties of stearic acid / MXene - Graphene oxide shape - Stabilized phase change material: Ascended phase transition temperature and hierarchical transition

To develop novel materials with active photothermal conversion and latent heat storage properties, the shape-stabilized phase change material was fabricated via self-assembly method employing stearic acid (SA) as heat storage medium, graphene oxide and MXene as hybrid matrix (GM) and photothermal conversion agent. The morphology, structure, properties and phase transition behavior were investigated by various techniques. The results shown that SA/GM has sandwich-like structure and SA is confined between matrix nanosheets in multiple crystallographic forms. Due to the superposition of host-guest interaction and intrinsic van der Waals force between nanosheets, the primary melting temperature of SA/GM climbs 27.7 °C approximately than that of SA, as well as the total latent heat decreases by 28.55%–30.85% compared with theoretical values. The confinement effect increases the crystallization activation energy of confined SA, and leads to the formation of non-phase transition layer, transitional confinement layer and proximate bulk layer. However, the above observations are applicable to fatty acids/GM, only the suppressed latent heat occurs in all GM-matrix composites. In addition, the SA/GM7 has excellent photothermal conversion efficiency, as high as 93.34%, and gradient latent heat storage capacity, 45.96 J g −1 at 74.43 °C and 91.19 J g −1 at 92.37 °C. Stearic acid/Mxene - graphene oxide (SA/GM) composite was fabricated though self-assembly method. The confined SA exists in multiple crystal forms and shows abnormal properties, including the ascended phase transition temperature, hierarchical phase transition and the formation of confined layer. The SA/GM presents excellent photothermal conversion efficiency and gradient heat storage/release performances. • SA/GM was self-assembled by the inherent forces of matrix nanosheets and host-guest interaction. • The main melting temperature of SA/GM increased by 27.7 °C approximately. • Non-phase change layer, transitional confinement layer and proximate bulk layer exist in SA/GM. • Ascended transition temperature and stratified phase transition are applicable to fatty acids/GM.

Biomimetic cell membrane-coated glucose/oxygen-exhausting nanoreactor for remodeling tumor microenvironment in targeted hypoxic tumor therapy

Hypoxia is a common feature within many types of solid tumors, which is closely associated with limited efficacy for tumor therapies. Moreover, the inability to reach hypoxic tumor cells that are distant from blood vessels results in tumor-targeting and penetrating drug delivery systems in urgent need. Here, glucose oxidase (GOX) and hypoxia-activated prodrug tirapazamine (TPZ) are loaded into photothermal conversion agent polydopamine (PDA) as the glucose/oxygen-exhausting nanoreactor named PGT. We further construct a tumor cell membrane-coated nanovesicle for the targeted delivery of PGT. This biomimetic nanovesicle exhibits significantly improved tumor-targeting and tumor-penetrating abilities. After internalization by the tumor cells, the loaded drug is quickly released in response to near-infrared (NIR) laser. The PGT nanoreactor can exhaust glucose and oxygen, and further enhance hypoxia within tumor, which efficiently inhibits hypoxic tumor by combining starvation therapy and hypoxia-activated chemotherapy. Mechanically, it is revealed that the nanoreactor significantly increases hypoxia level and downregulates the expression of hypoxia-inhibitory factor-1α (HIF-1α), thereby promoting T cell activation and macrophage polarization to remodel tumor immunosuppressive microenvironment. Therefore, this tumor microenvironment-regulable nanoreactor with sustainable and cascade targeted starvation-chemotherapy provides a novel insight into the treatment of hypoxic tumor.

Developing a Versatile Multiscale Therapeutic Platform for Osteosarcoma Synergistic Photothermo-Chemotherapy with Effective Osteogenicity and Antibacterial Capability.

Osteosarcoma is a devastating malignant neoplasm that seriously threatens human health. After an osteosarcoma resection, the simultaneous treatment of tumor recurrence, postoperative infection, and large bone loss remains a formidable challenge clinically. Herein, a versatile multiscale therapeutic platform (Fs-BP-DOX@PDA) is engineered based on NiTi alloys with versatile properties for near-infrared (NIR)-mediated osteosarcoma synergistic photothermo-chemotherapy, bone regeneration, and bacterial elimination. First, an intriguing method for fabricating groovelike micro-nanostructures (Fs-NiTi) through femtosecond laser direct writing to enhance osseointegration with strong contact guidance is proposed. Then, black phosphorus (BP) nanosheets as gratifying photothermal conversion agents, osteogenetic agents, and a drug delivery platform are decorated on Fs-NiTi to construct multiscale hierarchical structures (Fs-BP). Finally, the polydopamine (PDA) modification is utilized to enhance the photothermal performance, biocompatibility, and chemical stability of doxorubicin (DOX)-loaded Fs-BP and endow NIR/pH-dual-responsive DOX release properties. Fs-BP-DOX@PDA effectively induces tumor cell (Saos-2 and MDA-MB-231) death in vitro, completely eradicates osteosarcoma in mice, and observably promotes bone-regeneration bioactivity. Furthermore, it possesses prominent antibacterial efficiencies toward Staphylococcus aureus (99.2%) and Pseudomonas aeruginosa (99.6%). Overall, this work presents a smart comprehensive fabrication methodology to construct a versatile multiscale therapeutic platform for multimodal osteosarcoma treatment and biomedical tissue engineering.

Black porous silicon as a photothermal agent and immunoadjuvant for efficient antitumor immunotherapy

Photothermal therapy (PTT) in combination with other treatment modalities has shown great potential to activate immunotherapy against tumor metastasis. However, the nanoparticles (NPs) that generate PTT have served as the photothermal agent only. Moreover, researchers have widely utilized highly immunogenic tumor models to evaluate the immune response of these NPs thus giving over-optimistic results. In the present study black porous silicon (BPSi) NPs were developed to serve as both the photothermal agent and the adjuvant for PTT-based antitumor immunotherapy. We found that the poorly immunogenic tumor models such as B16 are more valid to evaluate NP-based immunotherapy than the widely used immunogenic models such as CT26. Based on the B16 cancer model, a cocktail regimen was developed that combined BPSi-based PTT with doxorubicin (DOX) and cytosine-phosphate-guanosine (CpG). BPSi-based PTT was an important trigger to activate the specific immunotherapy to inhibit tumor growth by featuring the selective upregulation of TNF-α. Either by adding a low dose DOX or by prolonging the laser heating time, a similar efficacy of immunotherapy was evoked to inhibit tumor growth. Moreover, BPSi acted as a co-adjuvant for CpG to significantly boost the immunotherapy. The present study demonstrates that the BPSi-based regimen is a potent and safe antitumor immunotherapy modality. Moreover, our study highlighted that tuning the laser heating parameters of PTT is an alternative to the toxic cytostatic to evoke immunotherapy, paving the way to optimize the PTT-based combination therapy for enhanced efficacy and decreased side effects. Statement of significanceTumor metastasis causes directly or indirectly more than 90% of cancer deaths. Combination of photothermal therapy (PTT), chemotherapy and immunotherapy based on nanoparticles (NPs) has shown great potential to inhibit distant and metastatic tumors. However, these NPs typically act only as photothermal agents and many of them have been evaluated with immunogenic tumor models. The present study developed black porous silicon working as both the photothermal conversion agent and the immunoadjuvant to inhibit distant tumor. It was recognized that the poorly immunogenic tumor model B16 is more appropriate to evaluate immunotherapy than the widely used immunogenic model CT26. The coordination mechanism of the PTT-based combination therapy regimen was discovered in detail, paving the way to optimize cancer immunotherapy for enhanced efficacy and decreased side effects.

Ultralight and flexible carbon-based phase change composites with high porosity for enhanced shape memory and photothermal conversion performance

Phase change materials (PCM) have limited practical application due to their high rigidity, poor photothermal conversion, low thermal conductivity, and insufficient drive capability. In this work, a flexible CF/(HO-BNNS@CuO)/PEG composite with high thermal conductivity and photothermal conversion capacity was prepared by using carbon foam (CF) as flexible supporting material, hydroxyl boron nitride nanosheets (HO-BNNS) as thermal conductivity filler, and copper oxide (CuO) as photothermal conversion agent. In CF/(HO-BNNS@CuO)/PEG containing 90 wt% PEG, the photothermal conversion storage efficiency reached 91.8% and the thermal conductivity was improved by 348% compared to pure PEG. It also presents excellent thermally driven shape memory properties (98 s) with the elastic characteristics of CF and the phase change characteristics of PEG. This provides a strategy to prepare flexible PCM with outstanding comprehensive performance, which helps to broaden the practical application of PCM. • Carbon foam (CF) has high elastic modulus and complete three-dimensional skeleton. • The photothermal conversion storage efficiency of CF/(HO-BNNS@CuO)/PEG(90) is as high as 91.8%. • CF/(HO-BNNS@CuO)/PEG(90) presents excellent thermally driven shape memory properties (98 s). • CF/(HO-BNNS@CuO)/PEG(90) has high heat storage capacity and fast heat transfer speed (1.12 W/m·K).

Antitumor Applications of Photothermal Agents and Photothermal Synergistic Therapies.

As a new tumor treatment strategy, photothermal therapy (PTT) has the advantages of accuracy, ease of administration, a high efficiency and low side effects. Photothermal transduction agents (PTAs) are the key factor which play an important role in PTT. The mechanism of PTT is discussed in detail. The photothermal conversion efficiency (PCE) can be improved by increasing the light absorption and reducing the light scattering of photothermal conversion agents. Additionally, non-radiative relaxation path attenuation can also promote energy conversion to obtain a higher value in terms of PCE. The structure and photothermal characteristics of various kinds of PTAs (metal materials, carbon-based nanomaterials, two-dimensional nanomaterials, and organic materials) were compared and analyzed. This paper reviews the antitumor applications of photothermal synergistic therapies, including PTT combined with immunotherapy, chemotherapy, and photodynamic therapy. This review proposes that these PTAs promote the development of photothermal synergistic therapies and have a great potential in the application of tumor treatment.

Functionalization of Se-Te Nanorods with Au Nanoparticles for Enhanced Anti-Bacterial and Anti-Cancer Activities.

The use of medical devices for therapeutic and diagnostic purpose is globally increasing; however, bacterial colonization on therapeutic devices can occur, causing severe infections in the human body. It has become an issue for public health. It is necessary to develop a nanomaterial based on photothermal treatment to kill toxic bacterial strains. Appropriately, high photothermal conversion and low-cost powerful photothermal agents have been investigated. Recently, gold nanocomposites have attracted great interest in biological applications. Here, we prepared rod-shaped Se-Te@Au nanocomposites of about 200 nm with uniform shape and surface-coated with gold nanoparticles for the first time showing high anti-bacterial and anti-cancer activities. Se-Te@Au showed proper structural consistency and natural resistance to bacterial and cancer cells. The strong absorption and high photothermal conversion efficacy made it a good photothermal agent material for the photothermal treatment of bacterial and cancer cells. The Se-Te@Au rod showed excellent anti-bacterial efficacy against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, with highest recorded inhibition zones of 25 ± 2 mm and 22 ± 2 mm, respectively. More than 99% of both types of strains were killed after 5 min with a near-infrared (NIR) laser at the very low concentration of 48 µg/mL. The Se-Te@Au rod’s explosion in HeLa cells was extensively repressed and demonstrated high toxicity at 100 µg/mL for 5 min when subjected to an NIR laser. As a result of its high photothermal characteristics, the exceptional anti-bacterial and anti-cancer effects of the Se-Te@Au rod are considerably better than those of other methods previously published in articles. This study could open a new framework for sterilization applications on the industrial level.

Anchoring branched Ag nano-islands on Au@CuxO mesoporous nanospheres as dual plasmonic absorbers for efficient photothermal conversion

Plasmonic semiconductor nanomaterials have been widely accepted as promising candidates for photothermal conversion, while the efficiency is yet to optimize. Herein, we report a facile synthesis of Au@CuxO mesoporous nanospheres anchored with branched Ag nano-islands on the surface and explore their applications as photothermal conversion agent. Due to the intimate hybridization of two materials, the Au@CuxO-Ag hybrid nanocomposites display a unique dual-plasmonic absorption that covers the visible-NIR range, benefiting the utilization efficiency of light energy. The synthesis is realized by reacting Au@CuxO with Ag+, the galvanic replacement reaction between them enables a preferential depletion of Cu phase, leaving Ag and Cu2O as dominate crystal phases. The resulting hybrid nanocomposites are featured with a core-shell structure but incomplete coverage, as well as the mesoporous interior and dendritic outer shell. In addition to the enhanced photothermal conversion efficiency, the current nano-hybrids show excellent structural stability and no decay in conversion after five successive rounds of measurement. The advantages in both morphological and electronic structure aspects are discussed. The present study validates the promising synergetic use of distinct hot charge carriers originating from metal and semiconductor that are photoexcited in the same hybrid nanoparticle for photothermal conversion, shedding light on rational design of photothermal materials based on metal-semiconductor hybrid nanocomposites.

Genetically Engineered Cell Membrane Modified Conjugated Polymer Nanoparticles for NIR‐II Photothermal Therapy

AbstractTumor‐selective near infrared‐induced photothermal therapy is a successful approach for ablation of malignant and cancerous cells. In the NIR region, tissue penetration depth in the near‐infrared second region (NIR‐II, 1000–1700 nm) is deeper than that of the traditional near‐infrared first region (NIR‐I, 700–900 nm) for the lower scattering and absorption. However, there are few photothermal conversion agents (PCAs) in the NIR‐II. And these PCAs are quickly identified by the immune system and rapidly cleared by the reticuloendothelial system (RES), leading to low accumulation in tumor, which prevents further advanced clinical practice. In this work, the conjugated polymer, PBTPBFTDPP, is prepared and assembled into nanoparticles (SPN). Then, the genetically engineered cell membranes are coated on the surface of SPN to obtain the positive targeting ability (SPN‐TF). The obtained SPN‐TF nanoparticles exhibit an excellent photothermal conversion ability, predominant targeting efficiency, and superb photothermal therapy for anticancer both in vitro and in vivo. These works will inspire more translational work on SPN for future clinical applications.

Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency.

Tumor immunotherapy is only effective in a fraction of patients due to a low response rate and severe side effects, and these challenges of immunotherapy in clinics can be addressed through induction of immunogenic cell death (ICD). ICD is elicited from many antitumor therapies to release danger associated molecular patterns (DAMPs) and tumor‐associated antigens to facilitate maturation of dendritic cells (DCs) and infiltration of cytotoxic T lymphocytes (CTLs). The process can reverse the tumor immunosuppressive microenvironment to improve the sensitivity of immunotherapy. Nanostructure‐based drug delivery systems (NDDSs) are explored to induce ICD by incorporating therapeutic molecules for chemotherapy, photosensitizers (PSs) for photodynamic therapy (PDT), photothermal conversion agents for photothermal therapy (PTT), and radiosensitizers for radiotherapy (RT). These NDDSs can release loaded agents at a right dose in the right place at the right time, resulting in greater effectiveness and lower toxicity. Immunotherapeutic agents can also be combined with these NDDSs to achieve the synergic antitumor effect in a multi‐modality therapeutic approach. In this review, NDDSs are harnessed to load multiple agents to induce ICD by chemotherapy, PDT, PTT, and RT in combination of immunotherapy to promote the therapeutic effect and reduce side effects associated with cancer treatment.

Nontoxic silicene photothermal agents with high near-infrared absorption for disassembly of Alzheimer’s amyloid‑β fibrils

The disassembly and eliminating the amyloid-β (Aβ) aggregates has become an effective way to treat Alzheimer’s disease (AD). Herein, for the first time, the near-infrared (NIR) activated silicene nanosheets (SNSs) have been identified as an effective nontoxic photothermal conversion agent for irreversibly disassembly of the Aβ33–42 aggregates. The SNSs synthesized by a combination of mild oxidation method and liquid exfoliation method possess good biocompatibility and biodegradability, and high near-infrared photothermal conversion capabilities. Under NIR light, the SNSs could disassemble the large and dense Aβ33–42 mature fibrils into short fibrils and even form thin films, leading to the degradation rate of 96.47%. The circular dichroism spectrum, fluorescent spectra, and nanostructure were analyzed to monitor the photothermal degradation of mature Aβ33–42 fibrils for elaborating the mechanism beneath. This study might provide a clue for developing potential therapeutic strategy for AD and related neurodegenerative diseases.

MoS2/LaF3 for enhanced photothermal therapy performance of poorly-differentiated hepatoma

Photothermal therapy (PTT) based on nanoparticle had been widely used to antitumor treatment. However, low photothermal conversion efficiency (PCE) is the main hurdle for antitumor treatment. To improve the PCE and gain ideal clinical the nanoparticle with higher photothermal conversion efficiency, we have developed a highly efficient solar absorber with MoS2/LaF3/ polydimethylsiloxane(PDMS) which can enhance the absorption of solar irradiation engergy, however, its photothermal effect irradiated by near-infrared light has not yet been investigated. The knowledge absence in photothermal effect will impede MoS2/LaF3/PDMS to be used for cancer therapy in clinic. In this study, we applied LaF3-loaded, MoS2-based photothermal conversion agents (PTAs) for improved photothermal cancer therapy. The study showed that the MoS2/LaF3 nanoflowers showed higher photothermal conversion efficiency (PCE, 42.5%) and could more effectively inhibit cancer cell proliferation compared to MoS2-based PTT agents in vitro. In vivo, the results further revealed that photothermal therapy using MoS2/LaF3 nanoflowers could significantly inhibit solid tumor growth. The study clearly demonstrated that MoS2/LaF3 could work at under low power NIR Laser in vitro and in vivo, resulting in a very impressive therapeutic effect in tumor-bearing mice. The MoS2/LaF3 nanoflowers will be prominent candidate nanoparticle for effective inhibiting tumor growth by photothermal therapy.

Application of metalloporphyrin sensitizers for the treatment or diagnosis of tumors

At present, metalloporphyrin compounds demonstrate three main uses as anticancer sensitizers: (1) photosensitizers, (2) photothermal conversion agents, and (3) ultrasound sensitizers. Developing efficient sensitizers for cancer with excellent controllability and biocompatibility is an important goal of oncology medicine. Because of the different structural diversity of anticancer sensitizers, such sensitizers are used for treating cancers by employing a variety of tumor treatment methods such as mature photodynamic therapy, commonly used clinically photothermal therapy and promising sonodynamic therapy. Among the many sensitizers, metalloporphyrin-complex sensitizers attract wide attention due to their excellent performance in tumor treatment and diagnosis. This review briefly describes some metalloporphyrin anticancer drugs and diagnostic agents related to photodynamic, photothermal and sonodynamic therapy, and discusses the roles of metal atoms in these drugs.

Bioactive NIR-II Light-Responsive Shape Memory Composite Based on Cuprorivaite Nanosheets for Endometrial Regeneration.

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near‐infrared (NIR‐II) light‐responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4O10) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l‐lactide‐co‐trimethylene carbonate) (PT) as shape memory building blocks is developed. The as‐prepared CUP/PT composite possesses excellent shape memory performance under NIR‐II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review.

Nanotechnology has opened up a world of possibilities for the treatment of brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver a variety of therapeutic agents, including drugs and nucleic acids. Nanoparticles may also be formulated to contain photosensitizers or, on their own, serve as photothermal conversion agents for phototherapy. Furthermore, nano-delivery agents can enhance the efficacy of contrast agents for improved brain imaging and diagnostics. However, effective nano-delivery to the brain is seriously hampered by the formidable blood–brain barrier (BBB). Advances in understanding natural transport routes across the BBB have led to receptor-mediated transcytosis being exploited as a possible means of nanoparticle uptake. In this regard, the oligopeptide Angiopep-2, which has high BBB transcytosis capacity, has been utilized as a targeting ligand. Various organic and inorganic nanostructures have been functionalized with Angiopep-2 to direct therapeutic and diagnostic agents to the brain. Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders.

Polydopamine nanoparticles with different sizes for NIR-promoted gene delivery and synergistic photothermal therapy

The combination of photothermal therapy and gene therapy has received increasing attention in tumor treatment. However, how to improve synergistic efficacy has become a new challenge. NIR light has a great potential in tumor treatment because of its considerable penetration depth and spatiotemporal controllability. Polydopamine is a popular photothermal conversion agent, which has desirable photothermal conversion ability and good biocompatibility. In this research, polydopamine-polyethyleneimine nanoparticles with diameters of 13 nm (SPPNPs) and 236 nm (LPPNPs) were prepared as gene carriers. The size of polydopamine nanoparticles had great effect on the complexes formation, photothermal conversion ability and gene transfection efficiency. After loading gene, the SPPNPs/gene and LPPNPs/gene complexes were about 60–80 nm and 240 nm respectively, indicating different styles of complexes formation. Both SPPNPs/gene and LPPNPs/gene complexes without NIR irradiation could achieve similar gene transfection efficiency as commercial lipofectamine 2000, while with lower cytotoxicity. Due to better photothermal conversion ability, the transfection level of LPPNPs/pGL-3 complexes increased to 4.5 times after NIR irradiation (2.6 W/cm2, 15 min), which ascribed to the quick escape of gene complexes from the endosome. The produced heat under NIR irradiation could also ablate tumor cells. So LPPNPs were chosen to deliver tumor suppressor gene p53 DNA to investigate the synergistic efficacy of gene/photothermal therapy. The tumor in KB tumor-bearing mice was almost eliminated after intratumoral injection, and the tumor inhibition efficacy of gene/photothermal synergistic therapy achieved to 99%. By combining NIR-promoted gene transfection and gene/photothermal synergistic therapy, the LPPNPs hold great promise in practical tumor treatment.