Synergistic Targeting and Efficient Photodynamic Therapy Based on Graphene Oxide Quantum Dot‐Upconversion Nanocrystal Hybrid Nanoparticles

Locating nanotherapeutics at the active sites, especially in the subcellular scale, is of great importance for nanoparticle‐based photodynamic therapy (PDT) and other nanotherapies. However, subcellular targeting agents are generally nonspecific, despite the fact that the accumulation of a nanoformulation at active organelles leads to better therapeutic efficacy. A PDT nanoformulation is herein designed by using graphene oxide quantum dots (GOQDs) with rich functional groups as both the supporter for dual targeting modification and the photosensitizer for generating reactive oxygen species, and upconversion nanoparticles (UCNs) as the transducer of excitation light. A tumor‐targeting agent, folic acid, and a mitochondrion‐targeting moiety, carboxybutyl triphenylphosphonium, are simultaneously attached onto the UCNs–GOQDs hybrid nanoparticles by surface modification, and a synergistic targeting effect is obtained for these nanoparticles according to both in vitro and in vivo experiments. More significant cell death and a higher extent of mitochondrion damage are observed compared to the results of UCNs–GOQDs nanoparticles with no or just one targeting moiety. Furthermore, the PDT efficacy on tumor‐bearing mice is also effectively improved. Overall, the current work presents a synergistic strategy to enhance subcellular targeting and the PDT efficacy for cancer therapy, which may also shed light on other kinds of nanotherapies.     

Flexible Cationic Nanoparticles with Photosensitizer Cores for Multifunctional Biomedical Applications

One challenge for multimodal therapy is to develop appropriate multifunctional agents to meet the requirements of potential applications. Photodynamic therapy (PDT) is proven to be an effective way to treat cancers. Diverse polycations, such as ethylenediamine‐functionalized poly(glycidyl methacrylate) (PGED) with plentiful primary amines, secondary amines, and hydroxyl groups, demonstrate good gene transfection performances. Herein, a series of multifunctional cationic nanoparticles (PRP) consisting of photosensitizer cores and PGED shells are readily developed through simple dopamine‐involving processes for versatile bioapplications. A series of experiments demonstrates that PRP nanoparticles are able to effectively mediate gene delivery in different cell lines. PRP nanoparticles are further validated to possess remarkable capability of combined PDT and gene therapy for complementary tumor treatment. In addition, because of their high dispersities in biological matrix, the PRP nanoparticles can also be used for in vitro and in vivo imaging with minimal aggregation‐caused quenching. Therefore, such flexible nanoplatforms with photosensitizer cores and polycationic shells are very promising for multimodal tumor therapy with high efficacy.     

Photosensitizer‐Conjugated Albumin−Polypyrrole Nanoparticles for Imaging‐Guided In Vivo Photodynamic/Photothermal Therapy

Conjugated polymers with strong absorbance in the near‐infrared (NIR) region have been widely explored as photothermal therapy agents due to their excellent photostability and high photothermal conversion efficiency. Herein, polypyrrole (PPy) nanoparticles are fabricated by using bovine serum albumin (BSA) as the stabilizing agent, which if preconjugated with photosensitizer chlorin e6 (Ce6) could offer additional functionalities in both imaging and therapy. The obtained PPy@BSA‐Ce6 nanoparticles exhibit little dark toxicity to cells, and are able to trigger both photodynamic therapy (PDT) and photothermal therapy (PTT). As a fluorescent molecule that in the meantime could form chelate complex with Gd³⁺, Ce6 in PPy@BSA‐Ce6 nanoparticles after being labeled with Gd³⁺ enables dual‐modal fluorescence and magnetic resonance (MR) imaging, which illustrate strong tumor uptake of those nanoparticles after intravenous injection into tumor‐bearing mice. In vivo combined PDT and PTT treatment is then carried out after systemic administration of PPy@BSA‐Ce6, achieving a remarkably improved synergistic therapeutic effect compared to PDT or PTT alone. Hence, a rather simple one‐step approach to fabricate multifunctional nanoparticles based on conjugated polymers, which appear to be promising in cancer imaging and combination therapy, is presented.     

Hybrid Nanomedicine Fabricated from Photosensitizer‐Terminated Metal–Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia‐Activated Cascade Chemotherapy

During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O₂‐consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia‐activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido‐/photosensitizer‐terminated UiO‐66 nanoscale metal–organic frameworks (UiO‐66‐H/N₃ NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered. Owing to the effective shielding of the nanoparticles, the stability of AQ4N is well preserved, highlighting the vital function of the nanocarriers. By virtue of strain‐promoted azide–alkyne cycloaddition, the nanocarriers are further decorated with a dense PEG layer to enhance their dispersion in the physiological environment and improve their therapeutic performance. Both in vitro and in vivo studies reveal that the O₂‐depleting PDT process indeed aggravates intracellular/tumor hypoxia that activates the cytotoxicity of AQ4N through a cascade process, consequently achieving PDT‐induced and hypoxia‐activated synergistic therapy. Benefiting from the localized therapeutic effect of PDT and hypoxia‐activated cytotoxicity of AQ4N, this hybrid nanomedicine exhibits enhanced therapeutic efficacy with negligible systemic toxicity, making it a promising candidate for cancer therapy.     

A Mesoporous Nanoenzyme Derived from Metal–Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy

Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (¹O₂). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal–organic frameworks (MOFs) is presented for in situ generation of endogenous O₂ to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese‐based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post‐modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O₂ generation through the catalytic reaction between the catalytic amount NE and the endogenous H₂O₂, the hypoxic tumor microenvironment is relieved. Thus, Ce6‐loaded NE serves as a H₂O₂‐activated oxygen supplier to increase the local O₂ concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T₂‐weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF‐derived mesoporous NE as a multifunctional theranostic agent in cancer therapy.     

Photosensitive Nanoparticles Combining Vascular‐Independent Intratumor Distribution and On‐Demand Oxygen‐Depot Delivery for Enhanced Cancer Photodynamic Therapy

In drug delivery, the poor tumor perfusion results in disappointing therapeutic efficacy. Nanomedicines for photodynamic therapy (PDT) greatly need deep tumor penetration due to short lifespan and weak diffusion of the cytotoxic reactive oxygen species (ROS). The damage of only shallow cells can easily cause invasiveness and metastasis. Moreover, even if the nanomedicines enter into deeper lesion, the effectiveness of PDT is limited due to the hypoxic microenvironment. Here, a deep penetrating and oxygen self‐sufficient PDT nanoparticle is developed for balanced ROS distribution within tumor and efficient cancer therapy. The designed nanoparticles (CNPs/IP) are doubly emulsified (W/O/W) from poly(ethylene glycol)‐poly(ε‐caprolactone) copolymers doped with photosensitizer IR780 in the O layer and oxygen depot perfluorooctyl bromide (PFOB) inside the core, and functionalized with the tumor penetrating peptide Cys‐Arg‐Gly‐Asp‐Lys (CRGDK). The CRGDK modification significantly improves penetration depth of CNPs/IP and makes the CNPs/IP arrive at both the periphery and hypoxic interior of tumors where the PFOB releases oxygen, effectively alleviating hypoxia and guaranteeing efficient PDT performance. The improved intratumoral distribution of photosensitizer and adequate oxygen supply augment the sensitivity of tumor cells to PDT and significantly improve PDT efficiency. Such a nanosystem provides a potential platform for improved therapeutic index in anticancer therapy.     

Efficacy Dependence of Photodynamic Therapy Mediated by Upconversion Nanoparticles: Subcellular Positioning and Irradiation Productivity

Singlet oxygen (¹O₂), as an important kind of reactive oxygen species (ROS) and main therapeutic agent in photodynamic therapy (PDT), only have a half‐life of 40 ns and an effective radius of 20 nm, which cause significant obstacles for improving PDT efficacy. In this work, novel upconversion nanoparticle (UCN)‐based nanoplatforms are developed with a minimized distance between UCNs and a photosensitizer, protoporphyrin IX (PpIX), and a controllable payload of PpIX, to enhance and control ROS production. The ability of the nanoplatform to target different subcellular organelles such as cell membrane and mitochondria is demonstrated via surface modification of the nanoplatform with different targeting ligands. The results show that the mitochondria‐targeting nanoplatforms result in significantly increased capability of both tumor cell killing and inhibition of tumor growth. Subcellular targeting of nanoparticles leads to the death of cancer cells in different manners. However, the efficiency of ROS generation almost have no influence on the tumor cell viability during the period of evaluation. These findings suggest that specific subcellular targeting of the nanoplatforms enhances the PDT efficacy more effectively than the increase of ROS production, and may shed light on future novel designs of effective and controllable PDT nanoplatforms.     

Integration of IR‐808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR‐excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR‐808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)‐functionalized silica layer is developed for PDT agent. The two booster effectors (dye‐sensitization and core–shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS₂ nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS₂ nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.     

Simulated Sunlight‐Mediated Photodynamic Therapy for Melanoma Skin Cancer by Titanium‐Dioxide‐Nanoparticle–Gold‐Nanocluster–Graphene Heterogeneous Nanocomposites

Simulated sunlight has promise as a light source able to alleviate the severe pain associated with patients during photodynamic therapy (PDT); however, low sunlight utilization efficiency of traditional photosensitizers dramatically limits its application. Titanium‐dioxide‐nanoparticle–gold‐nanocluster–graphene (TAG) heterogeneous nanocomposites are designed to efficiently utilize simulated sunlight for melanoma skin cancer PDT. The narrow band gap in gold nanoclusters (Au NCs), and staggered energy bands between Au NCs, titanium dioxide nanoparticles (TiO₂ NPs), and graphene can result in efficient utilization of simulated sunlight and separation of electron–hole pairs, facilitating the production of abundant hydroxyl and superoxide radicals. Under irradiation of simulated sunlight, TAG nanocomposites can trigger a series of toxicological responses in mouse B16F1 melanoma cells, such as intracellular reactive oxygen species production, glutathione depletion, heme oxygenase‐1 expression, and mitochondrial dysfunctions, resulting in severe cell death. Furthermore, intravenous or intratumoral administration of biocompatible TAG nanocomposites in B16F1‐tumor‐xenograft‐bearing mice can significantly inhibit tumor growth and cause severe pathological tumor tissue changes. All of these results demonstrate prominent simulated sunlight‐mediated PDT effects.     

Dual‐Stage Light Amplified Photodynamic Therapy against Hypoxic Tumor Based on an O2 Self‐Sufficient Nanoplatform

Tumor hypoxia severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a liposome‐based nanoparticle (designated as LipoMB/CaO₂) with O₂ self‐sufficient property for dual‐stage light‐driven PDT is demonstrated to address this problem. Through a short time irradiation, ¹O₂ activated by the photosensitizer methylene blue (MB) can induce lipid peroxidation to break the liposome, and enlarge the contact area of CaO₂ with H₂O, resulting in accelerated O₂ production. Accelerated O₂ level further regulates hypoxic tumor microenvironment and in turn improves ¹O₂ generation by MB under another long time irradiation. In vitro and in vivo experiments also demonstrate the superior competence of LipoMB/CaO₂ to alleviate tumor hypoxia, suppress tumor growth and antitumor metastasis with low side‐effect. The O₂ self‐sufficient LipoMB/CaO₂ nanoplatform with dual‐stage light manipulation is a successful attempt for PDT against hypoxic tumor.     

Nanoparticle‐Embedded Electrospun Fiber–Covered Stent to Assist Intraluminal Photodynamic Treatment of Oesophageal Cancer

Drug‐eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen‐producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO₂ with the endogenous H₂O₂ within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber‐covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced‐stage oesophageal cancer.     

Carrier-Free ATP-Activated Nanoparticles for Combined Photodynamic Therapy and Chemotherapy under Near-Infrared Light

The combination of photodynamic therapy (PDT) and chemotherapy (chemo-photodynamic therapy) for enhancing cancer therapeutic efficiency has attracted tremendous attention in the recent years. However, limitations, such as low local concentration, non-suitable treatment light source, and uncontrollable release of therapeutic agents, result in reduced combined treatment efficacy. This study considered adenosine triphosphate (ATP), which is highly upregulated in tumor cells, as a biomarker and developed ingenious ATP-activated nanoparticles (CDNPs) that are directly self-assembled from near-infrared photosensitizer (Cy-I) and amphiphilic Cd(II) complex (DPA-Cd). After selective entry into tumor cells, the positively charged CDNPs would escape from lysosomes and be disintegrated by the high ATP concentration in the cytoplasm. The released Cy-I is capable of producing single oxygen (¹O₂) for PDT with 808 nm irradiation and DPA-Cd can concurrently function for chemotherapy. Irradiation with 808 nm light can lead to tumor ablation in tumor-bearing mice after intravenous injection of CDNPs. This carrier-free nanoparticle offers a new platform for chemo-photodynamic therapy.     

A Novel Theranostic Nanoprobe for In Vivo Singlet Oxygen Detection and Real‐Time Dose–Effect Relationship Monitoring in Photodynamic Therapy

Singlet oxygen, as the main member of reactive oxygen species, plays a significant role in cancer photodynamic therapy. However, the in vivo real‐time detection of singlet oxygen remains challenging. In this work, a Förster resonance energy transfer (FRET)‐based upconversion nanoplatform for monitoring the singlet oxygen in living systems is developed, with the ability to evaluate the in vivo dose–effect relationship between singlet oxygen and photodynamic therapy (PDT) efficacy. In details, this nanoplatform is composed of core–shell upconversion nanoparticles (UCNPs), photosensitizer MC540, NIR dye IR‐820, and poly(acryl amine) PAA‐octylamine, where the UCNPs serve as an energy donor while IR‐820 serves as an energy acceptor. The nanoparticles are found to sensitively reflect the singlet oxygen levels generated in the tumor tissues during PDT, by luminescence intensity changes of UNCPs at 800 nm emission. Furthermore, it could also enable tumor treatment with satisfactory biocompatibility. To the best knowledge, this is the first report of a theranostic nanoplatform with the ability to formulate the in vivo dose–effect relationship between singlet oxygen and PDT efficacy and to achieve tumor treatment at the same time. This work might also provide an executable strategy to evaluate photodynamic therapeutic efficacy based on singlet oxygen pathway.     

A Highly‐Efficient Type I Photosensitizer with Robust Vascular‐Disruption Activity for Hypoxic‐and‐Metastatic Tumor Specific Photodynamic Therapy

Hypoxia severely impedes photodynamic therapy (PDT) efficiency. Worse still, considerable tumor metastasis will occur after PDT. Herein, an organic superoxide radical (O₂^??) nano‐photogenerator as a highly effcient type I photosensitizer with robust vascular‐disrupting efficiency to combat these thorny issues is designed. Boron difluoride dipyrromethene (BODIPY)‐vadimezan conjugate (BDPVDA) is synthesized and enwrapped in electron‐rich polymer‐brushes methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐ PPDA) to afford nanosized hydrophilic type I photosensitizer (PBV NPs). Owing to outstanding core–shell intermolecular electron transfer between BDPVDA and mPEG‐PPDA, remarkable O₂^?? can be produced by PBV NPs under near‐infrared irradiation even in severe hypoxic environment (2% O₂), thus to accomplish effective hypoxic‐tumor elimination. Simultaneously, the efficient ester‐bond hydrolysis of BDPVDA in the acidic tumor microenvironment allows vadimezan release from PBV NPs to disrupt vasculature, facilitating the shut‐down of metastatic pathways. As a result, PBV NPs will not only be powerful in resolving the paradox between traditional type II PDT and hypoxia, but also successfully prevent tumor metastasis after type I PDT treatment (no secondary‐tumors found in 70 days and 100% survival rate), enabling enhancement of existing hypoxic‐and‐metastatic tumor treatment.     

Photosensitizer and Autophagy Promoter Coloaded ROS‐Responsive Dendrimer‐Assembled Carrier for Synergistic Enhancement of Tumor Growth Suppression

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can trigger autophagy. However, little research is focused on whether there is a synergistic anticancer effect with PDT if extra autophagy promoter or inhibitor is added. Here, it is found that autophagy promotion significantly enhances the PDT activity to cancer cells. Based on this preliminary result, a ROS‐sensitive self‐assembled dendrimer nanoparticle is exploited as a carrier to codeliver an autophagy promoter (rapamycin, Rapa) and photosensitizer (phthalocyanine, Pc) to the tumor. After entrapped by cancer cells and irradiated by light, the ROS generated in PDT process of Pc can trigger nanoparticle destruction to release Rapa, thus initiating the autophagy process and remarkably enhancing the efficacy of PDT, leading to efficient tumor suppression.     

Iodine‐Rich Semiconducting Polymer Nanoparticles for CT/Fluorescence Dual‐Modal Imaging‐Guided Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) is a promising technique for cancer therapy, providing good therapeutic efficacy with minimized side effect. However, the lack of oxygen supply in the hypoxic tumor site obviously restricts the generation of singlet oxygen (¹O₂), thus limiting the efficacy of PDT. So far, the strategies to improve PDT efficacy usually rely on complicated nanosystems, which require sophisticated design or complex synthetic procedure. Herein, iodine‐rich semiconducting polymer nanoparticles (SPN‐I) for enhanced PDT, using iodine‐induced intermolecular heavy‐atom effect to elevate the ¹O₂ generation, are designed and prepared. The nanoparticles are composed of a near‐infrared (NIR) absorbing semiconducting polymer (PCPDTBT) serving as the photosensitizer and source of fluorescence signal, and an iodine‐grafted amphiphilic diblock copolymer (PEG‐PHEMA‐I) serving as the ¹O₂ generation enhancer and nanocarrier. Compared with SPN composed of PEG‐b‐PPG‐b‐PEG and PCPDTBT (SPN‐P), SPN‐I can enhance the ¹O₂ generation by 1.5‐fold. In addition, SPN‐I have high X‐ray attenuation coefficient because of the high density of iodine in PEG‐PHEMA‐I, providing SPN‐I the ability of use with computed tomography (CT) and fluorescence dual‐modal imaging. The study thus provides a simple nanotheranostic platform composed of two components for efficient CT/fluorescence dual‐modal imaging‐guided enhanced PDT.     

Enhancing Photodynamic Therapy through Resonance Energy Transfer Constructed Near‐Infrared Photosensitized Nanoparticles

Photodynamic therapy (PDT) is an important cancer treatment modality due to its minimally invasive nature. However, the efficiency of existing PDT drug molecules in the deep‐tissue‐penetrable near‐infrared (NIR) region has been the major hurdle that has hindered further development and clinical usage of PDT. Thus, herein a strategy is presented to utilize a resonance energy transfer (RET) mechanism to construct a novel dyad photosensitizer which is able to dramatically boost NIR photon utility and enhance singlet oxygen generation. In this work, the energy donor moiety (distyryl‐BODIPY) is connected to a photosensitizer (i.e., diiodo‐distyryl‐BODIPY) to form a dyad molecule ( RET‐BDP ). The resulting RET‐BDP shows significantly enhanced absorption and singlet oxygen efficiency relative to that of the acceptor moiety of the photosensitizer alone in the NIR range. After being encapsulated with biodegradable copolymer pluronic F‐127‐folic acid (F‐127‐FA), RET‐BDP molecules can form uniform and small organic nanoparticles that are water soluble and tumor targetable. Used in conjunction with an exceptionally low‐power NIR LED light irradiation (10 mW cm^?2), these nanoparticles show superior tumor‐targeted therapeutic PDT effects against cancer cells both in vitro and in vivo relative to unmodified photosensitizers. This study offers a new method to expand the options for designing NIR‐absorbing photosensitizers for future clinical cancer treatments.     

Glutathione Mediated Size‐Tunable UCNPs‐Pt(IV)‐ZnFe2O4 Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)‐platinum(IV) (Pt(IV))?ZnFe₂O₄, denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near‐infrared light can convert low energy photons to high energy ones, which act as the UV–vis source to simultaneously mediate the PDT effect and Fenton's reaction of ZnFe₂O₄ nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb³⁺ and Fe³⁺ in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X‐ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all‐in‐one imaging‐guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.     

Multifunctional Conjugated Polymer Nanoparticles for Image‐Guided Photodynamic and Photothermal Therapy

A multifunctional theranostic platform based on conjugated polymer nanoparticles (CPNs) with tumor targeting, fluorescence detection, photodynamic therapy (PDT), and photothermal therapy (PTT) is developed for effective cancer imaging and therapy. Two conjugated polymers, poly[9,9‐bis(2‐(2‐(2‐methoxyethoxy)ethoxy)‐ethyl)fluorenyldivinylene]‐alt‐4,7‐(2,1,3‐benzothiadiazole) with bright red emission and photosensitizing ability and poly[(4,4,9,9‐tetrakis(4‐(octyloxy)phenyl)‐4,9‐dihydro‐s‐indacenol‐dithiophene‐2,7‐diyl)‐alt‐co‐4,9‐bis(thiophen‐2‐yl)‐6,7‐bis(4‐(hexyloxy)phenyl)‐thiadiazolo‐quinoxaline] with strong near‐infrared absorption and excellent photothermal conversion ability are co‐loaded into one single CPN via encapsulation approach using lipid‐polyethylene glycol as the matrix. The obtained co‐loaded CPNs show sizes of around 30 nm with a high singlet oxygen quantum yield of 60.4% and an effective photothermal conversion efficiency of 47.6%. The CPN surface is further decorated with anti‐HER2 affibody, which bestows the resultant anti‐HER2‐CPNs superior selectivity toward tumor cells with HER2 overexpression both in vitro and in vivo. Under light irradiation, the PDT and PTT show synergistic therapeutic efficacy, which provides new opportunities for the development of multifunctional biocompatible organic materials in cancer therapy.     

Nanocomposite‐Based Photodynamic Therapy Strategies for Deep Tumor Treatment

Photodynamic therapy (PDT), as an emerging clinically approved modality, has been used for treatment of various cancer diseases. Conventional PDT strategies are mainly focused on superficial lesions because the wavelength of illumination light of most clinically approved photosensitizers (PSs) is located in the UV/VIS range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep‐seated tumors. The combination of PDT and nanotechnology is becoming a promising approach to fight against deep tumors. Here, the rapid development of new PDT modalities based on various smartly designed nanocomposites integrating with conventionally used PSs for deep tumor treatments is introduced. Until now many types of multifunctional nanoparticles have been studied, and according to the source of excitation energy they can be classified into three major groups: near infrared (NIR) light excited nanomaterials, X‐ray excited scintillating/afterglow nanoparticles, and internal light emission excited nanocarriers. The in vitro and in vivo applications of these newly developed PDT modalities are further summarized here, which highlights their potential use as promising nano‐agents for deep tumor therapy.