The bioengineered and multifunctional nanoparticles in pancreatic cancer therapy: Bioresponisive nanostructures, phototherapy and targeted drug delivery.

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.

Single-Photomolecular Nanotheranostics for Synergetic Near-Infrared Fluorescence and Photoacoustic Imaging-Guided Highly Effective Photothermal Ablation.

Multi-modality imaging-guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single-photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT-S) into an amphiphilic lipid, water-dispersible IT-S nanoparticles (IT-S NPs) are prepared. The obtained IT-S NPs have a very simple construction and possess ultra-stable near-infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual-modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT-S NPs are successfully visualized by NIR FL/PA dual-modal imaging. With the comprehensive in vivo imaging information provided by IT-S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT-S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.

Influence of natural convection on gold nanorods-assisted photothermal treatment of bladder cancer in mice.

Background: The thermally-induced urine flow can generate cooling that may alter the treatment outcome during hyperthermic treatments of bladder cancer. This paper investigates the effects of natural convection inside the bladder and at skin surface during gold nanorods (GNR) - assisted photothermal therapy (PTT) of bladder cancer in mice. Methods: 3D models of mouse bladder at orientations corresponding to the mouse positioned on its back, its side and its abdomen were examined. Numerical simulations were carried out for GNR volume fractions of 0.001, 0.005 and 0.01% and laser power of 0.2 and 0.3 W. Results: The obtained results showed that cooling due to natural convection inside the bladder and above the skin depends on the mouse orientation. For a mouse positioned on its back, on its side or on its abdomen, the maximum temperature achieved inside the tumour at 0.001% GNR volume fraction and 0.2 W laser power was 55.2°C, 50.0°C and 52.2°C, respectively compared to 56.8°C when natural convection was not considered. The average thermal gradients when natural convection was considered were also lower, suggesting a more homogenous temperature distribution. Conclusions: Natural convection inside the bladder can be beneficial but also detrimental to GNR-assisted PTT depending on the level of heating. At low levels of heating due to low GNR volume fraction and/or laser power, flow inside the bladder may dissipate heat from the targeted tissue; making the treatment ineffective. At high levels of heating due to high GNR volume fraction and/or laser power, cooling may prevent excessive thermal damage to surrounding tissues.

Specific Photothermal Ablation Therapy of Endometriosis by Targeting Delivery of Gold Nanospheres.

Endometriosis is difficult to treat since the side effects of the current therapeutic method and the high recurrence rate; thus, newer and safer therapeutic approaches are urgently needed. This work investigates the enhanced permeability and retention effect of CdTe quantum dots (QDs) and hollow gold nanospheres (HAuNS) in endometriosis to increase the delivery of HAuNS into lesion cells. The surface of HAuNS is successfully conjugated with a TNYL peptide that has specific affinity for the EphB4 receptor, which is a member of the Eph family of receptor tyrosine kinases. It is found that the EphB4 receptor is overexpressed in endometriosis lesions. The data indicate that both QDs and HAuNS can efficiently accumulate in endometriotic lesions through permeable vessels and the TNYL-conjugated HAuNS (TNYL-HAuNS) accumulate more via the interaction with EphB4. The specific photothermal ablation therapy based on TNYL-HAuNS significantly inhibits the growth of the endometriotic volume and induces the atrophy and degeneration of ectopic endometrium with no detectable toxicity to the normal organs. The level of TNF-α and estradiol also significantly decreases in the endometriotic lesions, indicating that the treatment enables a recovery from hormonal imbalance and inflammatory injury. This work can be a valuable reference for future endometriosis therapy.

Gold nanorod-mediated near-infrared laser ablation: in vivo experiments on mice and theoretical analysis at different settings.

PURPOSE: The aim of the present study was the in vivo assessment of the effects of gold nanorod (AuNR)-mediated laser ablation (LA) of flank xenograft tumours. We investigated: the differences between intra-tumoural (TIT) and surface tumoural temperature (TS); the influence of AuNRs concentration and laser power (P) on both these temperatures and on tumour regression. Lastly, experimental data were used to validate a theoretical model developed to predict the effects of AuNR-mediated LA. MATERIALS AND METHODS: Thirty-two nude mice were treated using near-infra-red light at two P, 3 d after injecting increasing AuNR doses. TIT and TS were recorded during the procedure by two thermocouples, one located within the tumour and the other one on the skin adjacent to the tumour. Tumour regression was assessed 2 d after near-infra-red exposure via Xenogen imaging. A three-dimensional temperature map was obtained by finite element modelling. RESULTS: TIT and TS difference is substantial when AuNRs are injected. Moreover, the maximum temperature reached is strongly influenced by both P and AuNR concentration. Tumours heated above 55 °C experienced regression. Good agreement between experimental and theoretical TIT was found (maximum difference of 4 °C). CONCLUSIONS: Data show significant influence of P and AuNR concentration on the temperatures reached during AuNR-mediated LA of solid tumours. TS and TIT difference increases with AuNRs concentration. Simulated temperatures agree quite well with experimental data. Together, these results represent the first step towards a rationally designed strategy to select the most promising laser settings and AuNRs concentration to improve solid tumour treatment outcomes.

Development of Man-rGO for Targeted Eradication of Macrophage Ablation.

This study was aimed to develop and evaluate a smart nanosystem that targeted photothermal ablation of inflammatory macrophages in atherosclerotic plaque. Mannosylated-reduced graphene oxide (Man-rGO) was synthesized using three step procedures: (1) preparation of ox-GOs, (2) microwave-assisted synthesis of PEI-rGOs, and (3) mannosylation of PEI-rGO using reductive amination reaction (Man-rGOs). The ζ-potential of Man-rGO that signifies electrophoretic mobility of the charged surface was examined using Zetasizer Nano ZS. The effects of Man-rGO on the cell viability was evaluated using LDH assay and AlamarBlue assay. The targeting efficacy of Man-rGO was assessed using the cellular uptake rate by M2-polarized (i.e., which is induced by IL-4) macrophage. The effects of NOMela loaded in Man-rGO on the enhancement of phagocytosis were evaluated by examining the phagocytic clearance rate of zymosan-FITC particles. The microwave-assisted reduction of GOs was adapted for a facile synthesis of polyethylenimine-reduced GO (PEI-rGO). The mannose functionalization (Man-rGO) of PEI-rGO produced a greater number of amide linkages formed by reductive amination reaction between PEI-rGO and mannose. The ζ-potential of PEI-rGO was +30.6 ± 3.3 mV, whereas that of Man-rGO was down to +13.1 ± 3.8 mV upon interaction with mannose mainly due to the conjugation of mannose on the PEI-rGO surface. Near-infrared (NIR) irradiation increased the temperature of Man-rGO solution to around 45 °C, suggesting that Man-rGO is more potent than ox-GO or rGO in photothermal ablation activity triggered by NIR laser irradiation (808 nm). All testing formulations at the concentrations up to 10 µg/mL exerted less than 10% of membrane disintegration. For AlamarBlue study, more than 90% of cell viability were maintained at the concentrations (up to 10 µg/mL) of all tested formulations. The fluorescent microscopy images of cells after 1 h incubation demonstrated that Man-rGO were mainly accumulated at the subcellular level where the mannose receptors were overexpressed. The cell viability of macrophages significantly decreased upon exposure to Man-rGO irradiated with NIR, but no changes were observed from that of mast cells (for mast cells, 98.3 ± 0.3%; for macrophages, 67.8 ± 1.3%, p < 0.01), indicating that Man-rGO achieved enhanced targetability toward mannose receptor mediated cellular uptake. N-Nitrosomelatonin (NOMela) loaded in macrophage exerted enhanced phagocytic activity. It was concluded that the enhanced photothermal ablation activity of Man-rGO triggered by NIR laser irradiation was mediated through their targetability toward overexpressed mannose receptor, a marker of M2-phenotype of macrophage. The results of this study supported that Man-rGO can serve as an efficient platform for the targeted therapy against atherosclerosis.

Gadolinium-conjugated gold nanoshells for multimodal diagnostic imaging and photothermal cancer therapy.

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, gadolinium-conjugated gold nanoshells are engineered and it is demonstrated that they enhance contrast for magnetic resonance imaging, X-ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation.

A Ligand-Directed Spatial Regulation to Structural and Functional Tunability in Aggregation-Induced Emission Luminogen-Functionalized Organic-Inorganic Nanoassemblies.

Aggregation-induced emission luminogen (AIEgen)-functionalized organic-inorganic hybrid nanoparticles (OINPs) are an emerging category of multifunctional nanomaterials with vast potential applications. The spatial arrangement and positioning of AIEgens and inorganic compounds in AIEgen-functionalized OINPs determine the structures, properties, and functionalities of the self-assembled nanomaterials. In this work, a facile and general emulsion self-assembly tactic for synthesizing well-defined AIEgen-functionalized OINPs is proposed by coassembling alkane chain-functionalized inorganic nanoparticles with hydrophobic organic AIEgens. As a proof of concept, the self-assembly and structural evolution of plasmonic-fluorescent hybrid nanoparticles (PFNPs) from concentric circle to core shell and then to Janus structures is demonstrated by using alkane chain-modified AuNPs and AIEgens as building blocks. The spatial position of AuNPs in the signal nanocomposite is controlled by varying the alkane ligand length and density on the AuNP surface. The mechanism behind the formation of various PFNP nanostructures is also elucidated through experiments and theoretical simulation. The obtained PFNPs with diverse structures exhibit spatially tunable optical and photothermal properties for advanced applications in multicolor and multimode immunolabeling and photothermal sterilization. This work presents an innovative synthetic approach of constructing AIEgen-functionalized OINPs with diverse structures, compositions, and functionalities, thereby championing the progressive development of these OINPs.

An injectable adhesive hydrogel for photothermal ablation and antitumor immune activation against bacteria-associated oral squamous cell carcinoma.

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.

MXene-Polydopamine-antiCEACAM1 Antibody Complex as a Strategy for Targeted Ablation of Melanoma.

Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.

Intraductal photothermal ablation: a noninvasive approach for early breast cancer treatment and prevention.

Background: Innovative treatment strategies for early-stage breast cancer (BC) are urgently needed. Tumors originating from mammary ductal cells present an opportunity for targeted intervention. Methods: We explored intraductal therapy via natural nipple openings as a promising non-invasive approach for early BC. Using functional Near-infrared II (NIR-II) nanomaterials, specifically NIR-IIb quantum dots conjugated with Epep polypeptide for ductal cell targeting, we conducted in situ imaging and photothermal ablation of mammary ducts. Intraductal administration was followed by stimulation with an 808 nm laser. Results: This method achieved precise ductal destruction and heightened immunological responses in the microenvironment. The technique was validated in mouse models of triple-negative BC and a rat model of ductal carcinoma in situ, demonstrating promising therapeutic potential for localized BC treatment and prevention. Conclusion: Our study demonstrated the effectiveness of NIR-II nanoprobes in guiding non-invasive photothermal ablation of mammary ducts, offering a compelling avenue for early-stage BC therapy.

Photothermal Catalytic Reduction and Bone Tissue Engineering Towards a Three-in-One Therapy Strategy for Osteosarcoma.

Osteosarcoma is one of the most dreadful bone neoplasms in young people, necessitating the development of innovative therapies that can effectively eliminate tumors while minimizing damage to limb function. An ideal therapeutic strategy should possess three essential capabilities: antitumor effects, tissue-protective properties, and the ability to enhance osteogenesis. In this study, self-assembled Ce-substituted molybdenum blue (CMB) nanowheel crystals are synthesized and loaded onto 3D-printed bioactive glass (CMB@BG) scaffolds to develop a unique three-in-one treatment approach for osteosarcoma. The CMB@BG scaffolds exhibit outstanding photothermally derived tumor ablation within the near-infrared-II window due to the surface plasmon resonance properties of the CMB nanowheel crystals. Furthermore, the photothermally synergistic catalytic effect of CMB promotes the rapid scavenging of reactive oxygen species caused by excessive heat, thereby suppressing inflammation and protecting surrounding tissues. The CMB@BG scaffolds possess pro-proliferation and pro-differentiation capabilities that efficiently accelerate bone regeneration within bone defects. Altogether, the CMB@BG scaffolds that combine highly efficient tumor ablation, tissue protection based on anti-inflammatory mechanisms, and enhanced osteogenic ability are likely to be a point-to-point solution for the comprehensive therapeutic needs of osteosarcoma.

Graphene in nanomedicine: A review on nano-bio factors and antibacterial activity.

Graphene-based nanomaterials possess potent antibacterial activity and have engrossed immense interest among researchers as an active armour against pathogenic microbes. A comprehensive perception of the antibacterial activity of these nanomaterials is critical to the fabrication of highly effective antimicrobial nanomaterials, which results in highly efficient and enhanced activity. These materials owing to their antimicrobial activity are utilized as nanomedicine against various pathogenic microbes. The present article reviews the antimicrobial activity of graphene and its analogs such as graphene oxide, reduced graphene oxide as well as metal, metal oxide and polymeric composites. The review draws emphasis on the effect of various nano-bio factors on the antibacterial capability. It also provides an insight into the antibacterial properties of these materials along with a brief discussion on the discrepancies in their activities as evidenced by the scientific communities. In this way, the review is expected to shed light on future research and development in graphene-based nanomedicine.

18F-fluorodeoxyglucose (18F-FDG) Functionalized Gold Nanoparticles (GNPs) for Plasmonic Photothermal Ablation of Cancer: A Review.

The meeting and merging between innovative nanotechnological systems, such as nanoparticles, and the persistent need to outperform diagnostic-therapeutic approaches to fighting cancer are revolutionizing the medical research scenario, leading us into the world of nanomedicine. Photothermal therapy (PTT) is a non-invasive thermo-ablative treatment in which cellular hyperthermia is generated through the interaction of near-infrared light with light-to-heat converter entities, such as gold nanoparticles (GNPs). GNPs have great potential to improve recovery time, cure complexity, and time spent on the treatment of specific types of cancer. The development of gold nanostructures for photothermal efficacy and target selectivity ensures effective and deep tissue-penetrating PTT with fewer worries about adverse effects from nonspecific distributions. Regardless of the thriving research recorded in the last decade regarding the multiple biomedical applications of nanoparticles and, in particular, their conjugation with drugs, few works have been completed regarding the possibility of combining GNPs with the cancer-targeted pharmaceutical fluorodeoxyglucose (FDG). This review aims to provide an actual scenario on the application of functionalized GNP-mediated PTT for cancer ablation purposes, regarding the opportunity given by the 18F-fluorodeoxyglucose (18F-FDG) functionalization.

Efficient improvement in chemo/photothermal synergistic therapy against lung cancer using Bi@Au nano-acanthospheres.

Novel highly hydrophilic and biocompatible bismuth nanospheres with gold nanoparticles growing outside (Bi@Au nano-acanthospheres, Bi@Au NASs) were synthesized through a simple procedure, which demonstrated to be a promising photothermal agent owing to the ultrahigh photothermal conversion efficiency (η = 46.6 %). The as-prepared Bi@Au NASs showed excellent blood compatibility and fairly low cytotoxicity to human lung cancer A549 cells, as well as efficient photothermal ablation (PTA) therapy induced by a near-infrared laser. Under the 808 nm laser radiation, the tumour temperature could be elevated by ∼25 °C high enough to kill the cancer cells. Moreover, the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded in Bi@Au NASs with a loading content as high as 16.78 % and released under a pH sensitive release profile, a characteristic beneficial for intravenous delivery of DOX into cancer cells for chemotherapy. The presence of the Bi element enabled Bi@Au NASs to act as a favourable computed tomography (CT) contrast medium for CT imaging-guided tumour treatment. Compared with cancer treatment through either photothermal therapy or chemotherapy, the chemo-photothermal synergistic therapy using Bi@Au NASs as both a photothermal agent and a drug carrier has efficiently enhanced the in vitro and in vivo therapeutic effects in cancer treatment.

Functionalized biomimetic nanoparticles combining programmed death-1/programmed death-ligand 1 blockade with photothermal ablation for enhanced colorectal cancer immunotherapy.

Immune checkpoint blockade therapy targeting programmed death-1 (PD-1) or its major ligand programmed death-ligand 1 (PD-L1) has achieved remarkable success in the treatment of several tumors, including colorectal cancer. However, the efficacy of PD-1/PD-L1 inhibitors is limited in some colorectal cancers within the immunosuppressive tumor microenvironment (such as when there is a lack of immune cell infiltration). Herein, anti-PD-L1 functionalized biomimetic polydopamine-modified gold nanostar nanoparticles (PDA/GNS@aPD-L1 NPs) were developed for synergistic anti-tumor treatment by combining PD-1/PD-L1 blockade with photothermal ablation. PDA/GNS@aPD-L1 NPs were prepared by encapsulating photothermal nanoparticles (polydopamine-modified gold nanostar, PDA-GNS) with cell membrane isolated from anti-PD-L1 single-chain variable fragment (scFv) over-expressing cells. In addition to disrupting PD-1/PD-L1 immunosuppressive signals, the anti-PD-L1 scFv on the membrane of PDA/GNS@aPD-L1 NPs was conducive to the accumulation of PDA-GNS at tumor sites. Importantly, the tumor photothermal ablation induced by PDA-GNS could reverse the immunosuppressive tumor microenvironment, thereby further improving the efficiency of PD-1/PD-L1 blockade therapy. In this study, the synthetized PDA/GNS@aPD-L1 NPs exhibited good biocompatibility, efficient photothermal conversion ability, and enhanced tumor-targeting ability. In vivo studies revealed that a PDA/GNS@aPD-L1 NP-based therapeutic strategy significantly inhibited tumor growth, and prolonged overall survival by further promoting the maturation of dendritic cells (DCs), increasing the infiltration of CD8+T cells, and decreasing the number of immunosuppressive cells (such as regulatory T cells and myeloid-derived suppressive cells). Collectively, the developed PDA/GNS@aPD-L1 NP-based therapeutic strategy combines PD-1/PD-L1 blockade with photothermal ablation, which could remodel the tumor microenvironment for effective clinical colorectal cancer therapy. STATEMENT OF SIGNIFICANCE: Immunosuppressive tumor microenvironment is the main challenge facing programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) blockade therapy. By encapsulating photothermal nanoparticles (polydopamine-modified gold nanostar, PDA-GNS) with cell membrane over-expressing anti-PD-L1 single-chain variable fragment, we constructed anti-PD-L1 functionalized biomimetic nanoparticles (PDA/GNS@aPD-L1 NPs). By specific binding to the PD-L1 present on tumor cells, PDA/GNS@aPD-L1 NPs could disrupt PD-1/PD-L1 immunosuppression signaling, and effectively deliver PDA-GNS targeting to tumor sites. Additionally, PDA-GNS-mediated local photothermal ablation of tumors promoted the release of tumor-associated antigens and thus activated anti-tumor immune responses. Meanwhile, hyperthermia facilitates immune cell infiltration by increasing tumor vascular permeability. Therefore, PDA/GNS@aPD-L1 NPs could sensitize tumors to PD-1/PD-L1 blockade therapy by remodeling the immunosuppressive tumor microenvironment, which provides a new strategy for tumor treatment.

State-of-the-art therapeutic strategies for targeting cancer stem cells in prostate cancer.

The development of new therapeutic strategies is on the increase for prostate cancer stem cells, owing to current standardized therapies for prostate cancer, including chemotherapy, androgen deprivation therapy (ADT), radiotherapy, and surgery, often failing because of tumor relapse ability. Ultimately, tumor relapse develops into advanced castration-resistant prostate cancer (CRPC), which becomes an irreversible and systemic disease. Hence, early identification of the intracellular components and molecular networks that promote prostate cancer is crucial for disease management and therapeutic intervention. One of the potential therapeutic methods for aggressive prostate cancer is to target prostate cancer stem cells (PCSCs), which appear to be a primary focal point of cancer metastasis and recurrence and are resistant to standardized therapies. PCSCs have also been documented to play a major role in regulating tumorigenesis, sphere formation, and the metastasis ability of prostate cancer with their stemness features. Therefore, the current review highlights the origin and identification of PCSCs and their role in anti-androgen resistance, as well as stemness-related signaling pathways. In addition, the review focuses on the current advanced therapeutic strategies for targeting PCSCs that are helping to prevent prostate cancer initiation and progression, such as microRNAs (miRNAs), nanotechnology, chemotherapy, immunotherapy, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing system, and photothermal ablation (PTA) therapy.

Microfluidic Formulation of Curcumin-Loaded Multiresponsive Gelatin Nanoparticles for Anticancer Therapy.

Current anticancer research shows that a combination of multiple treatment methods can greatly improve the killing of tumor cells. Using the latest microfluidic swirl mixer technology, combined with chemotherapy and photothermal-ablation therapy, we developed multiresponsive targeted antitumor nanoparticles (NPs) made of folate-functionalized gelatin NPs under 200 nm in size and with encapsulated CuS NPs, Fe3O4 NPs, and curcumin (Cur). By exploring gelatin's structure, adjusting its concentration and pH, and fine-tuning the fluid dynamics in the microfluidic device, the best preparation conditions were obtained for gelatin NPs with an average particle size of 90 ± 7 nm. The comparative targeting of the drug delivery system (DDS) was demonstrated on lung adenocarcinoma A549 cells (low level of folate receptors) and breast adenocarcinoma MCF-7 cells (high level of folate receptors). Folic acid helps achieve targeting and accurate delivery of NPs to the MCF-7 tumor cells. The synergistic photothermal ablation and curcumin's anticancer activity are achieved through infrared light irradiation (980 nm), while Fe3O4 is guided with an external magnetic field to target gelatin NPs and accelerate the uptake of drugs, thus efficiently killing tumor cells. The method described in this work is simple, easy to repeat, and has great potential to be scaled up for industrial production and subsequent clinical use.

A Polydopamine-Coated Platinum Nanoplatform for Tumor-Targeted Photothermal Ablation and Migration Inhibition.

In this work, Arg-Gly-Asp (RGD) peptide-coupled polydopamine-modified mesoporous platinum nanoparticles (mPt@PDA-RGD NPs) were developed for targeted photothermal therapy (PTT) and migration inhibition of SKOV-3 cells. mPt@PDA-RGD NPs with obvious core/shell structure demonstrated high photothermal performance under 808-nm near-infrared (NIR) laser irradiation. mPt@PDA-RGD NPs with favorable biocompatibility exhibited remarkable SKOV-3 inhibition ability under NIR laser irradiation. Moreover, compared to mPt@PDA NPs, the RGD-functionalized NPs achieved more tumor uptake and PTT performance, which was attributed to the specific interaction between RGD of NPs and αvß3 integrin overexpressed by SKOV-3. Importantly, cell scratch experiments indicated that the photothermal effect of mPt@PDA-RGD NPs can effectively inhibit the migration of surviving SKOV-3 cells, which was assigned to disturbance of the actin cytoskeleton of SKOV-3. Thus, mPt@PDA-RGD NPs presented great potential for targeted tumor photothermal ablation and migration inhibition.

Responsive nanomedicines enhanced by or enhancing physical modalities to treat solid cancer tumors: Preclinical and clinical evidence of safety and efficacy.

Nanomedicine has improved cancer treatment but not to the extent anticipated. Responsive nanomedicines enhanced by physical modalities (radiation, ultrasounds, alternating magnetic fields) or enhancing the activity of physical modalities such as radiotherapy to kill cancer represents an important approach in improving the safety and anticancer effectiveness. Importantly, the combined treatments have shown promise for the treatment of difficult to treat tumors, such as tumors that are resistant to chemotherapy (multi drug resistant, MDR) or radiotherapy and hypoxic tumors, and for the prevention of tumor metastasis. In this review, the mechanisms of responsive nanomedicines activity enhancement by physical means and vice versa are presented and preclinical and, most importantly, clinical evidence of the safety and efficacy of nanomedicines enhanced by or enhancing by physical modalities in treating solid tumors are critically discussed.