Photoacoustic Imaging Ability Research Articles

Review on Photoacoustic Monitoring after Drug Delivery: From Label-Free Biomarkers to Pharmacokinetics Agents.

Photoacoustic imaging (PAI) is an emerging noninvasive and label-free method for capturing the vasculature, hemodynamics, and physiological responses following drug delivery. PAI combines the advantages of optical and acoustic imaging to provide high-resolution images with multiparametric information. In recent decades, PAI's abilities have been used to determine reactivity after the administration of various drugs. This study investigates photoacoustic imaging as a label-free method of monitoring drug delivery responses by observing changes in the vascular system and oxygen saturation levels across various biological tissues. In addition, we discuss photoacoustic studies that monitor the biodistribution and pharmacokinetics of exogenous contrast agents, offering contrast-enhanced imaging of diseased regions. Finally, we demonstrate the crucial role of photoacoustic imaging in understanding drug delivery mechanisms and treatment processes.

Prussian Blue Nanohybridized Multicellular Spheroids as Composite Engraftment for Antioxidant Bone Regeneration and Photoacoustic Tomography.

Regulating the complex microenvironment after tooth extraction to promote alveolar bone regeneration is a pressing challenge for restorative dentistry. In this study, through modulating the mechanical properties of the cellular matrix, we guided various types of cells by self-organizing to form multicellular spheroids (MCSs) and hybridized MCSs with Prussian Blue nanoparticles (PBNPs) in the process. The constructed Prussian Blue nanohybridized multicellular spheroids (PBNPs@MCSs) with empowered antioxidant functions effectively reduced cell apoptosis under peroxidative conditions and exhibited enhanced ability to regulate the microenvironment and promote bone repair both in vitro and in vivo. In addition, the PBNPs@MCSs exhibited enhanced photoacoustic imaging ability to trace low doses of PBNPs. Therefore, the constructed PBNPs@MCSs based on the biomimetic hydrogel can be used as a form of an engraftment building block, with a greater potential for pro-bone repair application in the complex microenvironment of the oral cavity.

Photoacoustic imaging for non-invasive assessment of biomarkers of intestinal injury in experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is an often-lethal disease of the premature infant intestinal tract, exacerbated by significant diagnostic difficulties. In NEC, the intestine exhibits hypoperfusion and dysmotility, contributing to disease pathogenesis. However, these features cannot be accurately and quantitively assessed with current imaging modalities. We have previously demonstrated the ability of photoacoustic imaging (PAI) to non-invasively assess intestinal tissue oxygenation and motility in a healthy neonatal rat model. In this first-in-disease application, we evaluated NEC using PAI to assess intestinal health biomarkers in an experimental model of NEC. NEC was induced in neonatal rats from birth to 4-days. Healthy breastfed (BF) and NEC rat pups were imaged at 2- and 4-days. Intestinal tissue oxygen saturation was measured with PAI, and NEC pups showed significant decreases at 2- and 4-days. Ultrasound and PAI cine recordings were used to capture intestinal peristalsis and contrast agent transit within the intestine. Intestinal motility, assessed using computational intestinal deformation analysis, demonstrated significant reductions in both early and established NEC. NEC damage was confirmed with histology and dysmotility was confirmed by small intestinal transit assay. This preclinical study presents PAI as an emerging diagnostic imaging modality for intestinal disease assessment in premature infants. Necrotizing enterocolitis (NEC) is a devastating intestinal disease affecting premature infants with significant mortality. NEC presents significant clinical diagnostic difficulties, with limited diagnostic confidence complicating timely and effective interventional efforts. This study is an important foundational first-in-disease preclinical study that establishes the utility for PAI to detect changes in intestinal tissue oxygenation and intestinal motility with NEC disease induction and progression. This study demonstrates the feasibility and exceptional promise for the use of PAI to non-invasively assess oxygenation and motility in the healthy and diseased infant intestine.

PH-Activated Ce-Doped Molybdenum Oxide Nanoclusters for Tumor Microenvironment Responsive Photothermal and Chemodynamic Therapy.

Molybdenum-based nanomaterials have shown promise for anticancer treatment due to their strong photothermal and redox-activated capabilities. Herein, we have fabricated cerium-doped MoOx (Ce-MoOv) with tunable Mo/Ce molar ratios by a one-pot method and investigated their effect on chemodynamic therapy (CDT) and photothermal therapy (PTT). It is found that Ce-MoOv can self-assemble into nanoclusters in acidic conditions and the increasing Ce amount will generate oxygen vacancy defects and induce the valence change of Mo6+/Mo5+ and Ce4+/Ce3+, which leads to strong near-infrared absorption with high photothermal conversion efficiency of 71.31 and 49.86% for 808 and 1064 nm. Other than photothermal conversion, the materials demonstrate pH-/glutathione (GSH)-activated photoacoustic (PA) imaging capability in vitro. In addition, Ce-MoOv acts as a CDT reagent capable of converting endogenous H2O2 to two types of reactive oxygen species (•OH, 1O2) while depleting GSH. Ce-MoOv demonstrates an excellent therapeutic effect against HCT116 cells and effectively reduces the intracellular GSH level and significantly increases the number of reactive radicals under 1064 nm laser irradiation as compared with the no-laser group in vitro. This work provides a new paradigm using lanthanide-doped polymetallic oxides for pH-/GSH-responsive photothermal/chemodynamic therapy with PA imaging ability.

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000–1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Melanin theranostic nanoplatform as an efficient drug delivery system for imaging-guided renal fibrosis therapy

As renal fibrosis nanotherapeutics, the endogenous biomaterial melanin not only has natural biocompatibility and biodegradability but also has inherent photoacoustic imaging ability and certain anti-inflammatory effects. These properties determine that melanin can not only as a carrier of medication but also track the biodistribution and renal uptake of drugs in vivo by photoacoustic imaging in real-time. Curcumin is a natural compound with biological activity, which has excellent ROS scavenging ability and good anti-inflammatory property. These materials appear more advantages in the development of nanoscale diagnostic and therapeutic platforms for future clinical translation. Herein, this study developed curcumin-loaded melanin nanoparticles (MNP-PEG-CUR NPs) as an efficient medication delivery system for photoacoustic imaging guidance renal fibrosis treatment. The nanoparticles are about 10 nm in size, exhibit good renal clearance efficiency, excellent photoacoustic imaging ability, and good in vitro and in vivo biocompatibility. These preliminary results indicated that MNP-PEG-CUR have clinically applicable potential as a therapeutic nanoplatform for renal fibrosis.

Bismuth Oxychloride Nanomaterials Fighting for Human Health: From Photodegradation to Biomedical Applications

Environmental pollution and various diseases seriously affect the health of human beings. Photocatalytic nanomaterials (NMs) have been used for degrading pollution for a long time. However, the biomedical applications of photocatalytic NMs have only recently been investigated. As a typical photocatalytic NM, bismuth oxychloride (BiOCl) exhibits excellent photocatalytic performance due to its unique layered structure, electronic properties, optical properties, good photocatalytic activity, and stability. Some environmental pollutants, such as volatile organic compounds, antibiotics and their derivatives, heavy metal ions, pesticides, and microorganisms, could not only be detected but also be degraded by BiOCl-based NMs due to their excellent photocatalytic and photoelectrochemical properties. In particular, BiOCl-based NMs have been used as theranostic platforms because of their CT and photoacoustic imaging abilities, as well as photodynamic and photothermal performances. However, some reviews have only profiled the applications of dye degradation, hydrogen or oxygen production, carbon dioxide reduction, or nitrogen fixation of BiOCl NMs. There is a notable knowledge gap regarding the systematic study of the relationship between BiOCl NMs and human health, especially the biomedical applications of BiOCl-based NMs. As a result, in this review, the recent progress of BiOCl-based photocatalytic degradation and biomedical applications are summarized, and the improvement of BiOCl-based NMs in environmental and healthcare fields are also discussed. Finally, a few insights into the current status and future perspectives of BiOCl-based NMs are given.

Metal-polyphenol-coordinated nanomedicines for Fe(II) catalyzed photoacoustic-imaging guided mild hyperthermia-assisted ferroustherapy against breast cancer

Ferroustherapy has gained great attention for anti-cancer treatment in recent years. Enlightened by temperature-mediated Fenton reaction in industrial waste water removal, we designed a iron-based polyphenol-coordinated nanomedicines for mild hyperthermia-assisted anti-cancer ferroustherapy. In brief, Fe-GA@BSA nanoparticles was synthesized by self-assembly and sorafenib (SRF) was loaded into Fe-GA@BSA to establish Fe-GA@BSA-SRF nanomedicines. The result nanomedicines can induce ferroptosis in cancer cells by accelerating Fenton reaction. And the photothermal effect of Fe-GA@BSA-SRF was used for mild hyperthermia-assisted ferroustherapy. The nanomedicines performs good anti-cancer therapeutic efficacy by inducing the production of ROS and inhibiting glutathione peroxidase 4 (GPX4) expression in vitro and in vivo. Besides, the broad absorption of Fe-GA@BSA-SRF in near infrared region endows it with photoacoustic imaging ability. This study provides ideas about rational design on iron-based nanoparticles for anti-cancer ferroustherapy.

Mn(II)-directed dual-photosensitizers co-assemblies for multimodal imaging-guided self-enhanced phototherapy

Phototherapy has attracted increasing attention in cancer therapy owing to its non-invasive nature, high spatiotemporal selectivity, and negligible side effects. However, a single photosensitizer often exhibits poor photothermal conversion efficiency or insufficient reactive oxygen species (ROS) productivity. Even worse, the ROS can be consumed by tumor overexpressed reductive glutathione, resulting in severely compromised phototherapy. In this paper, we prepared a MnII-coordination driven dual-photosensitizers co-assemblies (IMCP) for imaging-guided self-enhanced PDT/PTT. Specifically, a photothermal agent indocyanine green (ICG), a photodynamic agent chlorin e6 (Ce6), and a transition metal ion (MnII/III) were chosen to synthesize the nanodrug via coordination-driven co-assembly. The as-prepared IMCP exhibited extremely high photosensitizer payload (96 wt%), excellent physiological stability, and outstanding tumor accumulation. Moreover, the existence of MnII not only assists the nanostructure formation but also could competitively coordinate with GSH to minimize the unnecessary ROS consumption, thus improving PDT efficiency. Meanwhile, benefiting from the intrinsic fluorescence, photoacoustic imaging ability of photosensitizers, and the MRI contrast potential of MnII/III, IMCP exhibited superior imaging potential for guiding tumor phototherapy. By changing the excitation wavelength suitably, IMCP could realize the switch between PTT and PDT. In short, the dual-PSs co-assembled nanotheranostic has great potential for multi-modal imaging guided phototherapy.

Learned spectral decoloring enables photoacoustic oximetry

The ability of photoacoustic imaging to measure functional tissue properties, such as blood oxygenation sO_2, enables a wide variety of possible applications. sO_2 can be computed from the ratio of oxyhemoglobin HbO_2 and deoxyhemoglobin Hb, which can be distuinguished by multispectral photoacoustic imaging due to their distinct wavelength-dependent absorption. However, current methods for estimating sO_2 yield inaccurate results in realistic settings, due to the unknown and wavelength-dependent influence of the light fluence on the signal. In this work, we propose learned spectral decoloring to enable blood oxygenation measurements to be inferred from multispectral photoacoustic imaging. The method computes sO_2 pixel-wise, directly from initial pressure spectra S_{text {p}_0}(lambda , mathbf {x}), which represent initial pressure values at a fixed spatial location mathbf {x} over all recorded wavelengths lambda. The method is compared to linear unmixing approaches, as well as pO_2 and blood gas analysis reference measurements. Experimental results suggest that the proposed method is able to obtain sO_2 estimates from multispectral photoacoustic measurements in silico, in vitro, and in vivo.

NIR-controlled HSP90 inhibitor release from hollow mesoporous nanocarbon for synergistic tumor photothermal therapy guided by photoacoustic imaging.

Photothermal therapy (PTT) has been widely studied for tumor therapy. However, the clinical transformation of PTT has encountered significant challenges in tumor recurrence, because the uneven hyperthermia in tumor tissues can result in the survival of cancer cells in the lower temperature regions close to blood vessels (as the blood flow can dissipate the localized heat). It is therefore important for clinical treatments to retain the excellent therapeutic efficiency of PTT at relatively low temperatures. In this article, innocuous hollow mesoporous carbon spheres (HMCS) with a high photothermal conversion efficiency were obtained by a one-pot synthesis method. After modification with DSPE-PEG, the HMCS-PEG exhibited a superior stability in biomedia, which is beneficial for further biological applications. Interestingly, combined with hydrophobic gambogic acid (GA) which can downregulate heat shock protein 90 (HSP90), the HMCS-PEG-GA system showed a significant NIR-enhanced tumor therapeutic effect in vitro and in vivo under mild temperature conditions (∼43 °C), and the combination index (CI) value of HMCS-PEG-GA was found to be 0.72. Meanwhile, this nano-system possessed good photothermal imaging and photoacoustic imaging abilities. Guided by the photoacoustic imaging signal, HMCS-PEG-GA showed enormous potential for use in accurate tumor diagnosis and mild-temperature PPT treatment applications, which is very important for clinical transformation of this nano-system.

Cyanine-Assisted Exfoliation of Covalent Organic Frameworks in Nanocomposites for Highly Efficient Chemo-Photothermal Tumor Therapy.

Covalent organic frameworks (COFs) have received considerable interest because of their advanced applications. However, their low dispersibility and aqueous stability are intractable issues limiting their biomedical application. To address the issue, water-dispersible nanocomposites (COF@IR783) produced through the assembly of cyanines and COFs are proposed and prepared. Therefore, a strategy of "killing three birds with one stone" is developed. First, the nanocomposites exhibit superior dispersibility and aqueous stability compared to COFs. The nanocomposites have a nanosized morphology and negative charges, which are in favor of improving the blood circulation and enhanced permeability and retention-mediated tumor-targeting delivery therapy for in vivo application. Second, the nanocomposites have enhanced photothermal therapy (PTT) ability in the near-infrared region compared to cyanines. The nanocomposites also have a photoacoustic imaging ability, which can guide the antitumor therapy in vivo. Lastly, the nanocomposites can be further used as drug-delivery carriers for loading the anticancer cis-aconityl-doxorubicin (CAD) prodrug. In comparison with individual PTT or chemotherapy, the combination of PTT and chemotherapy achieved with COF@IR783@CAD synergistically induced the death of cancer cells in vitro, and an intravenous injection of COF@IR783@CAD in mice resulted in significant tumor ablation. This work indicates that the dispersibility and aqueous stability of COFs can be appropriately overcome through a rational design and can further expand the biomedical applications of COFs.

Effects of gold nanoprism-assisted human PD-L1 siRNA on both gene down-regulation and photothermal therapy on lung cancer

Gold nanoprisms (GNPs) have been broadly studied for the potential applications in both imaging and treatment on tumors due to their special characteristics. Herein we reported that a new nanoplatform GNPs@PSS/PDADMAC-siRNA (GNPs-siRNA) was designed and fabricated by sequentially coating the GNPs with poly (sodium 4-styrenesulfonate) (PSS) and poly (-diallyldimethylammonium chloride) (PDADMAC) to carry small interfering RNA (siRNA). Human program death-ligand 1 (PD-L1) was recently known to be crucial for cancer cell survival through the intrinsic signaling activities, besides serving as an important checkpoint gene in immune system. We successfully attached the human PD-L1 siRNA to the surface of GNPs@PSS/PDADMAC to obtain the GNPs-hPD-L1 siRNA nanoplatform. Real Time Cellular Analysis (RTCA) assay demonstrated that GNPs-hPD-L1 siRNA exhibited remarkable capacity to inhibit the proliferation of human lung cancer cells. Subsequent in vitro and in vivo experiments verified that the GNPs-hPD-L1 siRNA not only functioned as a carrier for siRNA delivery to down-regulate the hPD-L1 expression, but also served for photoacoustic (PA) imaging and photothermal agents for photothermal therapy (PTT) in both human lung cancer cells and human lung cancer cells-derived tumors. Our findings could be expected to provide an innovative direction for future clinical transformation application. Statement of SignificanceTo our knowledge, this is the first paper related to the hPD-L1 siRNA delivery combined with the gold nanoparticles, especially the gold nanoprisms. The as-prepared GNPs-hPD-L1 siRNA nanoplatform not only functioned as a carrier for siRNA delivery to down-regulate the PD-L1 expression, but also acted as photothermal agents for theranostic effects in both human lung cancer cells and human lung cancer cells-derived tumors.The as-prepared GNPs-hPD-L1 siRNA nanoplatform could knock down human PD-L1 gene expression, which caused the inhibition on proliferation of human lung cancer cell in vitro or in vivo.The as-prepared GNPs-hPD-L1 siRNA nanoplatform possessed excellent photoacoustic imaging ability and photothermal therapy effects.

NIR- and thermo-responsive semi-interpenetrated polypyrrole nanogels for imaging guided combinational photothermal and chemotherapy

Versatile, multifunctional nanomaterials for theranostic approaches in cancer treatment are highly on demand in order to increase therapeutic outcomes. Here, we developed thermo-responsive nanogels equipped with the efficient near-infrared (NIR) transducing polymer polypyrrole (PPY) for combinational photothermal and chemotherapeutic therapy along with photoacoustic imaging ability. Long-term stability and water-dispersibility of PPY was achieved using semi-interpenetration method for in situ polymerization of PPY into hydrophilic thermo-responsive nanogels. The semi-interpenetrated nanogels of spherical shape and with hydrodynamic sizes of around 200 nm retained the temperature response behaviour and exhibit excellent photothermal transducing abilities in the NIR region. The PPY nanogels served as photoacoustic contrast agents, which allowed determination of biodistribution profiles ex vivo. In addition, we developed a new method for biodistribution determination based on the photothermal response of the nanogels with an accuracy down to 12.5 μg/mL. We examined the ability of the nanogels as photothermal agents and drug delivery systems in vitro and in vivo. We showed that they efficiently inhibit tumor growth with combinational effects of chemotherapeutics and photothermal treatment. Our work encourages further exploration of nanogels as functional stabilizing matrix for photothermal transducers and their application as drug delivery devices in combination with photothermal therapy and imaging.

Assessment of Age-related Oxygenation Changes in Calf Skeletal Muscle by Photoacoustic Imaging: A Potential Tool for Peripheral Arterial Disease.

Peripheral artery disease is often asymptomatic, and various imaging and nonimaging techniques have been used for assessment and monitoring treatments. This study is designed to demonstrate the ability of photoacoustic imaging to noninvasively determine changes in tissue oxygenation that occur in mice's hind limb skeletal muscle as they age. Mice from two age cohorts were scanned bilaterally with a pulsed laser. The photoacoustic signal was unmixed to generate a parametric map of estimated oxygen saturation and then overlaid on grayscale ultrasound images. Tissue oxygenation measured in young and old mice was compared. Photoacoustic imaging visually and quantitatively showed the decrease in skeletal muscle oxygenation that occurs with age. Percent tissue oxygenation decreased from 30.2% to 3.5% (p < 0.05). This reduction corresponded to reduced fractional area of oxygenation, which decreased from 60.6% to 6.0% (p < 0.05). The change in oxygenation capacity of the still active vascular regions was insignificant (p > 0.05). Intrasubject, intra-, and interobserver comparisons showed low variability in measurements, exhibited by high regression and intraclass correlations exceeding 0.81 for all ages. The decrease in oxygenation detected by photoacoustic imaging paralleled the known oxygenation decrease observed in aging tissues, demonstrating that photoacoustic imaging can assess age-related changes in a mouse calf muscle. These intramuscular changes could potentially act as a strong diagnostic marker for peripheral artery disease. This study thus opens the doors for a novel, affordable, noninvasive method of evaluation free of radiation or exogenous material.

Renal Clearable Bi-Bi2S3 Heterostructure Nanoparticles for Targeting Cancer Theranostics.

Recent development of precise nanomedicine has aroused an overwhelming interest in integration of diagnosis and treatment for cancers. Designing renal-clearable and targeting nanoparticles (NPs) has specific cancer theranostic implications and remains a challenging task. In this work, the ultrasmall folic acid (FA) and bovine serum albumin-modified Bi-Bi2S3 heterostructure nanoparticles NPs (Bi-Bi2S3/BSA&FA NPs) with excellent computed tomography (CT) and photoacoustic imaging abilities and outstanding photothermal performances were synthesized in an aqueous phase route via a simple method. Bi-Bi2S3/BSA&FA NPs have the following criteria: (i) Bi-Bi2S3/BSA&FA NPs with heterostructure possess better stability than Bi NPs and higher Bi content than Bi2S3 NPs, which are conducive to the enhancement of CT imaging effect; (ii) Bi-Bi2S3/BSA&FA NPs with FA molecules on the surface could target the tumor site effectively; (iii) Bi-Bi2S3/BSA&FA NPs could inhibit tumor growth effectively under 808 nm laser irradiation; (iv) ultrasmall Bi-Bi2S3/BSA&FA NPs could be cleared through kidney and liver within a reasonable time, avoiding a long-term retention/toxicity. Therefore, the renal clearable Bi-Bi2S3/BSA&FA NPs are a promising agent for targeting cancer theranostics.

Hollow mesoporous carbon nanospheres for imaging-guided light-activated synergistic thermo-chemotherapy.

Carbon-based light-activated materials can absorb optical energy to generate photoacoustic (PA) signals for imaging or transduce optical photons to thermal energy, which holds great promise for biomedical applications. Herein, we synthesize hollow and mesoporous carbon nanospheres (HMCNs) with uniform size on a large scale. The properties of hollow cavity and mesoporous structures make the HMCNs achieve high drug loading (480 mg DOX per g HMCNs). The present intense near infrared (NIR) absorbance achieves excellent photoacoustic imaging ability and photothermal conversion efficacy (32.0%). More interestingly, the encapsulated drugs can have a triggered release under NIR irradiation. The investigations in vitro and in vivo demonstrate that HMCNs have excellent biocompatibility, and accumulate in tumors by the enhanced permeability and retention (EPR) effect. Moreover, under NIR irradiation, in vivo evaluation shows that HMCNs can perform strong PA imaging, and induce great tumor inhibition by the combination of chemotherapy and PTT under the guidance of photoacoustic imaging. The present study provides new insight for design of novel biocompatible light-activated carbons for cancer nanotheranostics.

A smart off-on copper sulfide photoacoustic imaging agent based on amorphous-crystalline transition for cancer imaging.

By exploiting the amorphous-crystalline transition of CuS, which results in greatly increased absorption throughout the entire near-infrared region, a novel smart off-on CuS photoacoustic imaging agent with good photostability and low cost is developed. More importantly, the photoacoustic imaging ability of CuS can be effectively activated by body temperature for in vivo cancer imaging.

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging.

Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)-poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ∼38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.

Multifunctional polycationic photosensitizer conjugates with rich hydroxyl groups for versatile water-soluble photodynamic therapy nanoplatforms.

Photodynamic therapy (PDT) has already shown immense potential in antitumor fields due to its low systemic toxicity and negligible drug resistance. However, the clinical application of current photosensitizers is still restricted by the low singlet oxygen yield or insolubility. Herein, series of star-like hydroxyl-rich polycations (Pc-PGEA/Pc) with flanking phthalocyanine (Pc) were proposed for effective water-soluble photosensitizers. The designed Pc-PGEA/Pc polymers consist of one Pc core and four ethanolamine and Pc-difunctionalized poly(glycidyl methacrylate) arms. The strong π-π stacking and hydrophobicity of introduced Pc units drive the amphipathic Pc-PGEA/Pc polymers to self-assemble into well-defined cationic nanoparticles. Such Pc-PGEA/Pc nanoparticles present impressive photodynamic therapy effects under moderate irradiation and remarkable photoacoustic imaging (PAI) ability. These kinds of nanoparticles also exhibit good performance as gene vectors. The PAI ability given by the proper wavelength absorbance of Pc units provides one promising method for PAI-guided combined antitumor therapy. The present work would contribute valuable information for the development of new strategies of visible antitumor therapy.