Thermosensitive Liposomes Research Articles

Development of Radiolabeled Probes with Improved Imaging Contrast by Releasing Urinary Excretable Radiolabeled Compounds from Thermosensitive Liposomes in the Blood.

In this study, thermosensitive liposomes (TSLs) encapsulating urinary excretable radiolabeled compounds were developed. We considered that the release of the radiolabeled compounds from the TSLs in the blood by heating the blood in peripheral tissues can achieve rapid clearance of radioactivity, resulting in improved imaging contrast. To demonstrate the hypothesis, classical TSLs mainly composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine with a phase transition temperature of 41 °C were used. The optimal composition of TSLs was determined by an in vitro release test using [111In]In-diethylenetriaminepentaacetic acid (DTPA)-encapsulated liposomes, which showed that the cholesterol content drastically changed the release characteristics of classical TSLs. In the biodistribution experiments, [111In]In-DTPA was significantly released from the TSLs in the blood when the tails of mice were heated at 43 °C. The tumor-to-blood ratio of the heated group was three times higher than that of the nonheated group, and accumulation in normal tissues of the heated group was lower than that of the nonheated group. These results demonstrate the usefulness of the method using TSLs to encapsulate urinary excretable radiolabeled compounds for improving imaging contrast.

Effect of different injection strategies considering intravenous injection on combination therapy of magnetic hyperthermia and thermosensitive liposomes

Abstract The combination therapy of magnetic hyperthermia and thermosensitive liposomes (TSL) is an emerging and effective cancer treatment method. The heat generation of magnetic nanoparticles (MNPs) due to an external alternating magnetic field can not only directly damage tumor cells, but also serves as a triggering factor for the release of doxorubicin from TSL. The aim of this study is to investigate the effects in the degree of tumor cell damage of two proposed injection strategies that consider intravenous administration. Since both MNPs and TSL enter the tumor region intravenously, this study establishes a biological geometric model based on an experiment-based vascular distribution. Furthermore, this study derives the flow velocity of interstitial fluid after coupling the pressure distribution inside blood vessels and the pressure distribution of interstitial fluid, which then provides the convective velocity for the calculation of subsequent nanoparticle concentration. Different injection strategies for the proposed approach are evaluated by drug delivery result, temperature distribution, and tumor cell damage. Simulation results demonstrate that the proposed delayed injection strategy after optimization can not only result in a wider distribution for MNPs and TSL due to the sufficient diffusion time, but also improves the distribution of the temperature and drug concentration fields for the overall efficacy of combination therapy.

Reprogramming the Tumor Immune Microenvironment Through Activatable Photothermal Therapy and GSH depletion Using Liposomal Gold Nanocages to Potentiate Anti-Metastatic Immunotherapy.

Cancer immunotherapy offers significant clinical benefits for patients with advanced or metastatic tumors. However, immunotherapeutic efficacy is often hindered by the tumor microenvironment's high redox levels, leading to variable patient outcomes. Herein, a therapeutic liposomal gold nanocage (MGL) is innovatively developed based on photo-triggered hyperthermia and a releasable strategy by combining a glutathione (GSH) depletion to remodel the tumor immune microenvironment, fostering a more robust anti-tumor immune response. MGL comprises a thermosensitive liposome shell and a gold nanocage core loaded with maleimide. The flexible shell promotes efficient uptake by cancer cells, enabling targeted destruction through photothermal therapy while triggering immunogenic cell death and the maturation of antigen-presenting cells. The photoactivated release of maleimide depletes intracellular GSH, increasing tumor cell sensitivity to oxidative stress and thermal damage. Conversely, GSH reduction also diminishes immunosuppressive cell activity, enhances antigen presentation, and activates T cells. Moreover, photothermal immunotherapy decreases elevated levels of heat shock proteins in tumor cells, further increasing their sensitivity to hyperthermia. In summary, MGL elicited a robust systemic antitumor immune response through GSH depletion, facilitating an effective photothermal immunotherapeutic strategy that reprograms the tumor microenvironment and significantly inhibits primary and metastatic tumors. This approach demonstrates considerable translational potential and clinical applicability.

Dual structure on-demand release chitosan-based coating film for peach preservation

After harvest, fruits and vegetables go through the stages of storage, transportation and sales, and how to regulate the role of preservative in different stages is an urgent problem to be solved. Herein, chitosan-stearic acid is synthesized, then interacting with trans-2-hexenal (E2H) to prepare nanoclusters. Subsequently, the temperature-sensitive liposomes were designed to encase E2H by using the special temperature-responsive open-chain phospholipids, and then combined with chitosan to obtain chitosan-based coating film for peach preservation. The thermosensitive liposomes were uniformly distributed, highly dispersed and spherical, which has excellent temperature response characteristics, and the release of active substances could be regulated in the temperature range of 10 °C-40 °C to achieve the effect of on-demand release. In addition, thermosensitive liposomes also have excellent antioxidant and antibacterial activities. Therefore, the obtained chitosan-based coating could maintain the freshness of peaches, improve the quality and extend the storage period of peaches. The edible chitosan coating and active preservative prepared in this study have potential application value in responsive intelligent active packaging.

Thermosensitive Liposomes for Gemcitabine Delivery to Pancreatic Ductal Adenocarcinoma.

Treatment of pancreatic ductal adenocarcinoma with gemcitabine is limited by an increased desmoplasia, poor vascularization, and short plasma half-life. Heat-sensitive liposomes modified by polyethylene glycol (PEG; PEGylated liposomes) can increase plasma stability, reduce clearance, and decrease side effects. Nevertheless, translation of heat-sensitive liposomes to the clinic has been hindered by the low loading efficiency of gemcitabine and by the difficulty of inducing hyperthermia in vivo. This study was designed to investigate the effect of phospholipid content on the stability of liposomes at 37 °C and their release under hyperthermia conditions; this was accomplished by employing a two-stage heating approach. First the liposomes were heated at a fast rate, then they were transferred to a holding bath. Thermosensitive liposomes formulated with DPPC: DSPC: PEG2k (80:15:5, mole%) exhibited minimal release of carboxyfluorescein at 37 °C over 30 min, indicating stability under physiological conditions. However, upon exposure to hyperthermic conditions (43 °C and 45 °C), these liposomes demonstrated a rapid and significant release of their encapsulated content. The encapsulation efficiency for gemcitabine was calculated at 16.9%. Additionally, fluorescent analysis during the removal of unencapsulated gemcitabine revealed an increase in pH. In vitro tests with BxPC3 and KPC cell models showed that these thermosensitive liposomes induced a heat-dependent cytotoxic effect comparable to free gemcitabine at temperatures above 41 °C. This study highlights the effectiveness of the heating mechanism and cell models in understanding the current challenges in developing gemcitabine-loaded heat-sensitive liposomes.

Versatile Thermo-Sensitive liposomes with HSP inhibition and Anti-Inflammation for synergistic Chemo-Photothermal to inhibit breast cancer metastasis

Photothermal therapy (PTT) is a prospective therapeutic method for breast cancer. However, excess inflammatory response induced by PTT may aggravate tumor metastasis. Meanwhile, the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. Therefore, to attenuate the PTT-induced inflammation and inhibit tumor metastasis, a folate receptor-targeted thermo-sensitive liposome (BI-FA-LP) co-loading Berberine (BBR) and Indocyanine green (ICG) was developed. BI-FA-LP utilized enhanced permeability and retention (EPR) effect and FA receptor-mediated endocytosis to selectively accumulate at tumor, reducing off-target toxicity during the treatment. After targeting to the tumor site, BBR and ICG were released from BI-FA-LP upon laser irradiation, and ICG showed good photothermal performance, while BBR inhibited HSP70 and HSP90 expression during PTT, exerting chemo-photothermal synergetic anti-tumor effect. Moreover, BBR could suppress the PTT induced inflammation, thus inhibiting tumor metastasis and ameliorating tissue injury. Thus, this versatile liposome provided a new strategy to enhance PTT and anti-inflammatory effects for breast cancer treatment.

Laser-enzyme dual responsive liposomes to regulate autophagy in synergy with phototherapy for melanoma treatment

Phototherapy can cause autophagy while killing tumour cells, leading to tumour recurrence and metastasis. Here, we constructed a laser and enzyme dual responsive nanodrug delivery system Tf-Te@CTSL-HCQ (TT@CH) to precisely regulate autophagy in synergy with phototherapy to inhibit the proliferation and metastasis of melanoma. Firstly, transferrin (Tf) was used as a nanoreactor to synthesise phototherapy agent Tf-Te by the biological template mineralisation method. Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system. Once arriving at the tumour site, TT@CH can be cleaved by FAP-α overexpressed on cancer-associated fibroblasts (CAFs), and release Tf-Te and HCQ. Then Tf-Te can target melanoma cells and exert PTT/PDT anti-tumour effect. What’s more, hyperpyrexia induced by PTT can further promote drugs release from TT@CH. Meanwhile, HCQ simultaneously inhibited autophagy of CAFs and melanoma cells, and down-regulated IL-6 and HMGB1 secretion, thus effectively inhibiting melanoma metastasis. Pharmacodynamic results exhibited the best anti-tumour effect of TT@CH with the highest tumour inhibition rate of 91.3%. Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.

Synergistic effects of thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy in breast cancer management: an orthotopic mouse model study.

Liposome formulations of the cancer drug doxorubicin have been developed to address the severe side effects that result from administration of this drug in a conventional formulation. Among them, thermosensitive liposomal doxorubicin presents enhanced tumor targeting and efficient drug release when combined with mild hyperthermia localized to the tumor site. Exploiting the radiosensitizing benefits of localized thermal therapy, the integration of radiation therapy with the thermally activated liposomal system is posited to amplify the anti-tumor efficacy. This study explored a synergistic therapeutic strategy that combines thermosensitive liposomal doxorubicin, mild hyperthermia, and radiotherapy, using an orthotopic murine model of breast cancer. The protocol of sequential multi-modal treatment, incorporating low-dose chemotherapy and radiotherapy, substantially postponed the progression of primary tumor growth in comparison to the application of monotherapy at elevated dosages. Improvements in unheated distant lesions were also observed. Furthermore, the toxicity associated with the combination treatment was comparable to that of either thermosensitive liposome treatment or radiation alone at low doses. These outcomes underscore the potential of multi-modal therapeutic strategies to refine treatment efficacy while concurrently diminishing adverse effects in the management of breast cancer, providing valuable insight for the future refinement of thermosensitive liposomal doxorubicin applications.

Three Birds with One Stone: Copper Ions Assisted Synergistic Cuproptosis/Chemodynamic/Photothermal Therapy by a Three-Pronged Approach.

Copper is indispensable to organisms, while its homeostatic imbalance may interference normal cellular physiological processes and even induce cell death. Artificially regulating cellular copper content provides a viable strategy to activate antineoplastic effect. In light of this, a copper ions homeostasis perturbator (CuP-CL) with cinnamaldehyde (Cin) packaging and thermosensitive liposome coating is reported. Following laser exposure, the doping of Cu2+ in polydopamine initiates enhanced photothermal therapy (PTT) and unlocks the outer layer of liposome, leading to the release of copper ions and Cin in tumor microenvironment with mild acidity and high glutathione (GSH) levels. The liberative Cu2+ can evoke cuproptosis and chemodynamic therapy (CDT). Meanwhile, leveraging the merits of H2O2 supply and GSH consumption, Cin serves as a tumor microenvironment regulator to amplify Cu2+ mediated cuproptosis and CDT. Additionally, the positive feedback effects of "laser-triggered PTT, PTT accelerates reactive oxygen species (ROS) generation, ROS amplifies lipid peroxide (LPO) accumulation, LPO mediates heat shock proteins (HSPs) clearance, down-regulated HSPs promote PTT" entailed the overall benefit to therapeutic outcomes. Both in vitro and in vivo results corroborate the remarkable antineoplastic performance of CuP-CL by the synergy of cuproptosis/CDT/PTT. Collectively, based on the three-pronged approach, this work plots a viable multimodal regimen for cancer therapy.

Decoding the effect of different tumor heterogeneities on thermosensitive liposome drug delivery during radiofrequency ablation: A novel heat and mass transfer perspective

Background and objectiveRadio-frequency ablation (RFA)-mediated thermosensitive liposomes (TSL) drug delivery promotes loco-regional drug delivery, simultaneously reducing systemic toxicity. However, the heterogeneous intratumoral microenvironment, such as non-uniformly distributed microvascular network, extracellular matrix, intracellular space, disproportionate blood flow through tumor microvessels, and disparate extracellular diffusion impedes the transport of intravenously administered TSL, significantly affecting therapeutic efficacy. The current study is focused on elucidating the effect of aforementioned tumor microenvironment heterogeneities on TSL drug delivery outcomes, which remains unexplored. MethodsDifferent tumor heterogeneities, namely blood flow, extracellular drug diffusion, microvascular, extracellular and intracellular volume fractions, and 3D brain tumor geometry, are extracted using advanced magnetic resonance imaging (MRI) techniques. The extracted patient-specific information is incorporated in the bioheat-fluid-mass transport coupled solver developed in OpenFOAM to numerically predict the effect of each heterogeneity on drug delivery efficacy and compare with homogeneous scenarios. ResultsA significant underestimation of 70–72% in free drug and TSL extracellular concentrations and 56% in intracellular drug concentration is observed when using homogeneous properties compared to complete heterogeneous. Further, microvascular and extracellular volume fractions significantly affect the drug distribution patterns of the four heterogeneities, with blood flow and drug diffusion contributing the least. ConclusionsThe current study highlights the need to incorporate patient-specific tumor microenvironment heterogeneities in future modeling studies to predict the therapeutic outcomes of hyperthermia-related drug delivery treatments.

Ultrasound-triggered in situ hydrogel formation for spinal disc repair

Over 600 million people suffer from lower back pain attributable to spinal disc degeneration. Treatments range from conservative physiotherapy to costly, invasive options like spinal fusion surgery. Injectable engineered materials may allow minimally invasive disc repair, but self-curing lacks process control, and optical in situ curing is depth-limited. We, therefore, propose ultrasound-triggered implant formation, enabling spatiotemporal control at clinically relevant tissue depths. We developed an anionic polysaccharide-based hydrogel, seeded with calcium-loaded thermosensitive liposomes. Focused ultrasound was used to heat this injectable precursor material to just above the lipid phase-transition temperature of 41 °C, inducing calcium release and ionically crosslinked network formation. Controlled heating was achieved by elevating the acoustic attenuation of the precursor solution with purified glass microspheres. The heating and gelation processes were controlled in real-time using thermometry and acoustic cavitation emissions. We optimized the ultrasound frequency and pressure amplitude to provide controlled heating with minimal cavitation. After these parameters were employed for ultrasound-mediated gelation, the rheological properties of the resultant gels were compared to literature values for native spinal disc material. Finally, in situ gel formation was evaluated in ex vivo bovine tail discs, from injection to mechanical assessments, confirming the ability to remotely trigger injectable disc-mimicking materials.

Spatiotemporal modeling of nano-delivered chemotherapeutics for synergistic microwave ablation cancer therapy

Background and objectiveThe effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved. Multiscale computational-based modeling frameworks, integrating different biophysical phenomena, have recently emerged as promising tools to decipher the mechanobiological events in combo therapies. The present study aims to develop a novel multiscale computational model of TSLs delivery following MWA implantation. MethodsDue to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform. ResultsResults indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors. ConclusionThis study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.

Eutectic Resolves Lysolipid Paradox in Thermoresponsive Liposomes.

A better molecular understanding of the temperature-triggered drug release from lysolipid-based thermosensitive liposomes (LTSLs) is needed to overcome the recent setbacks in developing this important drug delivery system. Enhanced drug release was previously rationalized in terms of detergent-like effects of the lysolipid monostearyl lysophosphatidylcholine (MSPC), stabilizing local membrane defects upon LTSL lipid melting. This is highly surprising and here referred to as the 'lysolipid paradox,' because detergents usually induce the opposite effect─they cause leakage upon freezing, not melting. Here, we aim at better answers to (i) why lysolipid does not compromise drug retention upon storage of LTSLs in the gel phase, (ii) how lysolipids can enhance drug release from LTSLs upon lipid melting, and (iii) why LTSLs typically anneal after some time so that not all drug gets released. To this end, we studied the phase transitions of mixtures of dipalmitoylphosphatidylcholine (DPPC) and MSPC by a combination of differential scanning and pressure perturbation calorimetry and identified the phase structures with small- and wide-angle X-ray scattering (SAXS and WAXS). The key result is that LTSLs, which contain the standard amount of 10 mol % MSPC, are at a eutectic point when they release their cargo upon melting at about 41 °C. The eutectic present below 41 °C consists of a MSPC-depleted gel phase as well as small domains of a hydrocarbon chain interdigitated gel phase containing some 30 mol % MSPC. In these interdigitated domains, the lysolipid is stored safely without compromising membrane integrity. At the eutectic temperature, both the MSPC-depleted bilayer and interdigitated MSPC-rich domains melt at once to fluid bilayers, respectively. Intact, fluid membranes tolerate much less MSPC than interdigitated domains─where the latter have melted, the high local MSPC content causes transient pores. These pores allow for fast drug release. However, these pores disappear, and the membrane seals again as the MSPC distributes more evenly over the membrane so that its local concentration decreases below the pore-stabilizing threshold. We provide a pseudobinary phase diagram of the DPPC-MSPC system and structural and volumetric data for the interdigitated phase.

Smart composite scaffold to synchronize magnetic hyperthermia and chemotherapy for efficient breast cancer therapy

Combination of different therapies is an attractive approach for cancer therapy. However, it is a challenge to synchronize different therapies for maximization of therapeutic effects. In this work, a smart composite scaffold that could synchronize magnetic hyperthermia and chemotherapy was prepared by hybridization of magnetic Fe3O4 nanoparticles and doxorubicin (Dox)-loaded thermosensitive liposomes with biodegradable polymers. Irradiation of alternating magnetic field (AMF) could not only increase the scaffold temperature for magnetic hyperthermia but also trigger the release of Dox for chemotherapy. The two functions of magnetic hyperthermia and chemotherapy were synchronized by switching AMF on and off. The synergistic anticancer effects of the composite scaffold were confirmed by in vitro cell culture and in vivo animal experiments. The composite scaffold could efficiently eliminate breast cancer cells under AMF irradiation. Moreover, the scaffold could support proliferation and adipogenic differentiation of mesenchymal stem cells for adipose tissue reconstruction after anticancer treatment. In vivo regeneration experiments showed that the composite scaffolds could effectively maintain their structural integrity and facilitate the infiltration and proliferation of normal cells within the scaffolds. The composite scaffold possesses multi-functions and is attractive as a novel platform for efficient breast cancer therapy.

T lymphocyte-derived immunogenic hybrid nanovesicles for immunosuppression reversion and boosted photothermal immunotherapy

Photothermal therapy (PTT) can mediate the immunogenic cell death (ICD) of tumors through photothermal transformation, thus releasing tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs) to stimulate the maturation of dendritic cells (DCs) and elicit the immune response against tumors. However, PTT-mediated upregulation of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) will cause the immune evasion of tumor cells and thus increases the immunosuppression of cytotoxic T lymphocytes (CTLs), resulting in restricted photothermal immune activation. Taking advantage of the high expression of programmed cell death protein 1 (PD-1) in T lymphocytes, we develop an immunogenic photothermal hybrid nanovesicle to reverse immunosuppression and enhance PTT-induced ICD. The hybrid vesicle (TMVL-I) is constructed by phospholipid bilayer fusion of T cell-derived membrane vesicle (TMV) with high PD-1 expression and the indocyanine green (ICG)-loaded thermosensitive liposome (L-I). TMVL-Is bind to the tumor cells with PTT-induced upregulation of PD-L1, effectively blocking the PD-1/PD-L1 pathway between CTLs and tumor cells, thus reversing PD-L1-mediated tumor immunosuppression and intensifying photothermal-induced ICD effects. These processes significantly induce the maturation of DCs and enhance the infiltration of CTLs into both primary and distal tumors and the activation of spleen CTLs, strongly inhibiting the growth of B16 xenograft tumors and greatly improving the survival rate of B16 xenograft mice. This work provides a feasible strategy for immunosuppressive microenvironment reprogramming-based combination therapy.

Harnessing the power of thermosensitive liposomes with gold nanoprisms and silica for controlled drug delivery in combined chemotherapy and phototherapy.

In recent years, the scientific community has tried to address the treatment of complex diseases such as cancer in a more appropriate and promising way. Regarding this and benefiting from the unique optical properties of gold nanoprisms (AuNPRs), the physicochemical properties of thermosensitive liposomes (TSLs), and the tunable drug encapsulation and release properties of silica nanoparticles (BioSi@NPs), this study has developed two nanoformulations. These nanoformulations have the potential to integrate chemotherapy and photothermal therapy within a single entity. Once their components were synthesized and characterized separately, two strategies were taken in order to develop these multifunctional nanoformulations: (1) covalent binding of AuNPRs to TSLs and (2) co-encapsulation of both components within BioSi@NPs, without modifying the optical and physicochemical properties of AuNPRs and TSLs. Finally, the suitability of both nanoformulations to carry and release hydrophilic drugs when triggered by a 1064 nm NIR laser has been explored by using the fluorescent probe 5(6)-carboxyfluorescein (CF) as a hydrophilic drug model. Different laser power and time of exposure were also tested evidencing that hydrophilic drugs were only released from TSLs in the presence of AuNPRs and that the drug release profile was dependent on the type of nanoformulation and irradiation conditions used. In conclusion, these multifunctional nanoformulations exhibit promising potential for controlled drug delivery in combined chemotherapy and phototherapy, with the capability to precisely control the release kinetics based on specific therapeutic needs.

Correction: Thermosensitive drug-loaded liposomes for photothermal and chemotherapeutic treatment of colon cancer

Correction for ‘Thermosensitive drug-loaded liposomes for photothermal and chemotherapeutic treatment of colon cancer’ by Haihua Zhou et al., Mater. Adv., 2024, 5, 2456–2469, https://doi.org/10.1039/D3MA01060K.

Design of multi-modal antenna arrays for microwave hyperthermia and 1H/1⁹F MRI monitoring of drug release.

This simulation-based study presented a novel hybrid RF antenna array designed for neck cancer treatment within a 7T MRI system. The proposed design aimed to provide microwave hyperthermia to release 19F-labeled anticancer drugs from thermosensitive liposomes, facilitating drug concentration monitoring through 19F imaging and enabling 1H anatomical imaging and MR thermometry for temperature control. The design featured a bidirectional microstrip for generating the magnetic |B1|-fields required for 1H and 19F MR imaging, along with a patch antenna for localized RF heating. The bidirectional microstrip was operated at 300 MHz and 280 MHz through the placement of excitation ports at the ends of the antenna and an asymmetric structure along the antenna. Additionally, a patch antenna was positioned at the center. Based on this setup, an array of six antennas was designed. Simulation results using a tissue-mimicking simulation model confirmed the intensity and uniformity of |B1|-fields for both 19F and 1H nuclei, demonstrating the suitability of the design for clinical imaging. RF heating from the patch antennas was effectively localized at the center of the cancer model. In simulations with a human model, average |B1|-fields were 0.21 μT for 19F and 0.12 μT for 1H, with normalized-absolute-average-deviation values of 81.75% and 87.74%, respectively. Hyperthermia treatment was applied at 120 W for 600 s, achieving an average temperature of 40.22°C in the cancer model with a perfusion rate of 1 ml/min/kg. This study demonstrated the potential of a hybrid antenna array for integrating 1H MR, 19F drug monitoring, and hyperthermia.

Thermosensitive drug-loaded liposomes for photothermal and chemotherapeutic treatment of colon cancer

Schematic of BiNSs/Met/5-FU@TSL for anti-tumor through “PTT-Chemo” combination therapy.

Immunoadjuvant-Modified Rhodobacter sphaeroides Potentiate Cancer Photothermal Immunotherapy.

Photothermal immunotherapy has become a promising strategy for tumor treatment. However, the intrinsic drawbacks like light instability, poor immunoadjuvant effect, and poor accumulation of conventional inorganic or organic photothermal agents limit their further applications. Based on the superior carrying capacity and active tumor targeting property of living bacteria, an immunoadjuvant-intensified and engineered tumor-targeting bacterium was constructed to achieve effective photothermal immunotherapy. Specifically, immunoadjuvant imiquimod (R837)-loaded thermosensitive liposomes (R837@TSL) were covalently decorated onto Rhodobacter sphaeroides (R.S) to obtain nanoimmunoadjuvant-armed bacteria (R.S-R837@TSL). The intrinsic photothermal property of R.S combined R837@TSL to achieve in situ near-infrared (NIR) laser-controlled release of R837. Meanwhile, tumor immunogenic cell death (ICD) caused by photothermal effect of R.S-R837@TSL, synergizes with released immunoadjuvants to promote maturation of dendritic cells (DCs), which enhance cytotoxic T lymphocytes (CTLs) infiltration for further tumor eradication. The photosynthetic bacteria armed with immunoadjuvant-loaded liposomes provide a strategy for immunoadjuvant-enhanced cancer photothermal immunotherapy.