Imaging-guided Photodynamic Therapy Research Articles

Correction: A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma

Correction for ‘A lipid droplet targeted fluorescent probe for high-efficiency image-guided photodynamic therapy of renal cell carcinoma’ by Ping Tan et al., Chem. Commun., 2021, DOI: 10.1039/d0cc07336a.

A lipid droplet specific fluorescent probe for image-guided photodynamic therapy under hypoxia.

Photodynamic therapy (PDT) is a potential strategy for many superficial, esophageal, intestinal, and bronchial cancer treatments, but its therapeutic effect is limited by a lack of specificity and the hypoxic tumor environment. It is necessary to develop novel photosensitizers (Ps) with organelles targeting and the ability to generate cytotoxic species under light irradiation without the presence of oxygen. Herein, we designed and synthesized a biocompatible fluorescent Ps CPNBD for lipid droplets (LDs) fluorescence (FL) image-guided PDT. CPNBD showed FL quenching in water but FL was significantly turned on by oil with a remarkable FL enhancement compared to that in aqueous solution. Due to its strong lipophilicity (Clog P of 7.96), CPNBD could specifically stain the LDs of human clear cell renal cell carcinoma (ccRCC) tumor cells and tissues with good photostability. Meanwhile, CPNBD could efficiently generate cytotoxic reactive oxygen species under low-power white-light irradiation, which could efficiently damage DNA via a PDT process with great tumor suppression ability in vitro and in vivo. Thus, this work provides a novel strategy for designing LD-targeting Ps with efficient image-guided PDT under the tumor hypoxic environment.

Enhancing near-infrared AIE of photosensitizer with twisted intramolecular charge transfer characteristics via rotor effect for AIE imaging-guided photodynamic ablation of cancer cells

Near-infrared (NIR) aggregation-induced emission (AIE) of previous organic photosensitizers is usually weak because of the competition between twisted intramolecular charge transfer (TICT) effect and AIE. Herein, we report a rational molecular design strategy to boost NIR AIE of photosensitizers and still to keep strong 1O2 production capacity via rotor effect. To this end, one new triphenylamine (TPA)-based AIE photosensitizer, TPAM-1, is designed to give strong ability to generate 1O2 but weak NIR fluorescence in the aggregate state due to the strong TICT effect. Another new TPA-based AIE photosensitizer, TPAM-2, is designed by introducing three p-methoxyphenyl units as rotors into the structure of TPAM-1 to modulate the competition between AIE and TICT. TPAM-1 and TPAM-2 exhibit stronger ability to generate 1O2 in the aggregate state than the commercial photosensitizer, Ce6. Furthermore, TPAM-2 gives much brighter NIR luminescence (25-times higher quantum yield) than TPAM-1 in the aggregate state due to the rotor effect. TPAM-2 with strong NIR AIE and 1O2 production capability was encapsulated by DSPE-PEG2000 to give good biocompatibility. The DSPE-PEG2000-encapsulated TPAM-2 nanoparticles show good cell imaging performance and remarkable photosensitive activity for killing HeLa cells. This work provides a new way for designing ideal photosensitizers for AIE imaging-guided photodynamic therapy.

Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo.

Multifunctional aggregation-induced emission nanoparticle for high-fidelity imaging of lipid droplets in living cells and its application in photodynamic therapy

Near-infrared (NIR) aggregation-induced emission (AIE) nanomaterials, with organelles targeted-imaging ability and effective reactive oxygen species (ROS) generation nature, are highly desirable photosensitizers (PSs) for fluorescence imaging-guided photodynamic therapy (PDT), but it remains challenging. Herein, a NIR AIE luminogens (AIEgens, TTI) was designed and synthesized using three-fragmentary assembly molecular engineering, which was used for intracellular lipid droplets (LDs) high-fidelity dynamic tracking (Pearson’s coefficient of 0.95) due to its strong lipophilic nature (ClogP of 8.34), large Stokes shifts (170 nm), excellent photostability and good biocompatibility. Meanwhile, TTI self-assembled nanoparticles with an average diameter of 196.57 nm exhibited extremely high-efficient singlet oxygen (1O2) generation efficiency (with up to 85.16% of quantum yield) in PBS solution. In addition, the TTI as a desired PS revealed good phototoxicity for living HepG2 cells under white light irradiation. Moreover, the live/dead cells co-staining image, flow cytometry and scratch wound healing assays indicated that TTI could effectively inhibit the proliferation and cause/induce cells apoptosis, which eventually led to the death of HepG2 cells. Therefore, this work provides a useful strategy for LDs-targeting molecular engineering and highlights the potential of organic nanoparticles PSs drug in biomedical and fluorescence imaging-guided PDT fields.

Molecular engineering to accelerate cancer cell discrimination and boost AIE-active type I photosensitizer for photodynamic therapy under hypoxia

The severe hypoxia in solid tumor and the accurate discrimination between cancer and normal cells gravely restrict the application of fluorescence imaging-guided photodynamic therapy (PDT), although this cancer-therapy modality has significant superiorities in terms of precise visualization of the location of photosensitizers (PSs) in tumor tissue as well as noninvasive and reliable treatment. A convenient and universal fluorescence system featuring Type I reactive oxygen species (ROS) based on free radicals, wide-spectrum cancer cell discrimination and distinctive aggregation-induced emission (AIE) characteristics could offer a feasible approach to resolve the problems above, which is yet extremely challenging. Herein, we propose a series of electron-rich anion-π+ AIE-active luminogens (AIEgens) fabricating increasingly stronger intermolecular charge transfer (ICT) state to promote highly efficient intersystem crossing for boosting Type I ROS generation. Moreover, MeOTPPM has priority to enter cancer cells with better plasma membrane permeability due to the strongest binding force with water molecules. This work serves as a pioneering reference for rationally constructing Type I-based purely organic PSs to overcome tumor hypoxia defects in PDT and selectively targeting and ablating cancer cells over normal cells without the aid of any extra cancer cell-specific targeting ligands.

Bright Aggregation-Induced Emission Nanoparticles for Two-Photon Imaging and Localized Compound Therapy of Cancers.

Photodynamic therapy (PDT), a noninvasive therapeutic strategy for cancer treatment, which always suffers from the low reactive oxygen species (ROS) yield of traditional organic dyes. Herein, we present lipid-encapsulated aggregation-induced emission nanoparticles (AIE NPs) that have a high quantum yield (23%) and a maximum two-photon absorption (TPA) cross-section of 560 GM irradiated by near-infrared light (800 nm). The AIE NPs can serve as imaging agents for spatiotemporal imaging of tumor tissues with a penetration depth up to 505 μm on mice melanoma model. Importantly, the AIE NPs can simultaneously generate singlet oxygen (1O2) and highly toxic hydroxyl radicals (•OH) upon irradiation with 800 nm irradiation for photodynamic tumor ablation. In addition, the AIE NPs can be effectively cleared from the mouse body after the imaging and therapy. This study provides a strategy to develop theranostic agents for cancer image-guided PDT with high brightness, superior photostability, and high biosafety.

Red AIE conjugated polyelectrolytes for long-term tracing and image-guided photodynamic therapy of tumors

Robust photosensitizers with strong red/NIR fluorescence, efficient reactive oxygen species (ROS) generation and high photostability are highly desired for photodynamic therapy (PDT). Herein, three novel red conjugated polyelectrolytes (CPEs) with tetraphenylethene and 2,1,3-benzothiadiazole on the main chains and triphenylphosphonium on the side chains are developed. These CPEs display apparent aggregation-induced emission feature and high fluorescence quantum yields in the aggregated state. They can target lysosome in HeLa cells for fluorescence bioimaging. By virtue of the good retention effect and high photostability, these CPEs show ultralong-term tracing performance of subcutaneous tumors, and the tumor site can still be visualized for 20 days after injection. Owing to their good biocompatibility and strong ROS generation ability, the image-guided PDT based on these CPEs can effectively inhibit the growth of subcutaneous tumor and significantly prolong the survival of tumor bearing mice. The H&E and IHC staining reveal that the PDT of these CPEs depress the proliferation of tumor cells, and promote apoptosis and necrosis process. These new CPEs may be employed both as fluorescent probes for in vitro and in vivo long-term tracing and as photosensitizers for image-guided PDT of tumors.

Dendritic organosilica nanospheres with large mesopores as multi-guests vehicle for photoacoustic/ultrasound imaging-guided photodynamic therapy

Photodynamic therapy (PDT) is a minimally invasive treatment strategy that uses photosensitizers and light in combination with oxygen to generate cytotoxic singlet oxygen (1O2) to kill cancer cells by necrosis or apoptosis. However, the treatment effects are still not satisfactory because of the tumor hypoxia and the PDT-induced oxygen consumption. Here, we have successfully synthesized dendritic mesoporous organosilica nanoparticles (MONs) with large center-radial pore structure that can be used to simultaneously encapsulate indocyanine green (ICG, <1 nm) and macromolecule catalase (CAT, 2.0 nm × 6.0 nm × 9.0 nm) to overcome the tumor hypoxia. Upon 808 nm laser irradiation, ICG as the organic NIR dye can generate highly cytotoxic singlet oxygen (1O2) and other reactive oxygen species (ROS) to kill cancer cells and realize photoacoustic (PA) imaging. The catalase can decompose the endogenous H2O2 in malignant cancerous cells into O2 bubble to simultaneously intensify the ultrasound (US) imaging signal and enhance PDT efficacy. These results indicate that the ICG-CAT@MONs holds great promise in multimodal photoacoustic / ultrasound image-guided tumor PDT therapy.

Smart Magnetic and Fluorogenic Photosensitizer Nanoassemblies Enable Redox-Driven Disassembly for Photodynamic Therapy.

Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy (PDT) of tumors. However, the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox-responsive magnetic and fluorogenic PS nanoassemblies (NP-RGD) synthesized via self-assembly of a cRGD- and disulfide-containing fluorogenic and paramagnetic small molecule (1-RGD) for fluorescence/magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small-molecule probe (2-RGD) and an organic PS (PPa-SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors.

Rational Design of a High-Performance Quinoxalinone-Based AIE Photosensitizer for Image-Guided Photodynamic Therapy.

Because light exhibits excellent spatiotemporal resolution, photodynamic therapy (PDT) is becoming a promising method for cancer treatment. However, in a single photosensitizer (PS), it remains a big challenge to achieve all key properties including effective singlet oxygen (1O2) production under long-wavelength laser and bright near-infrared (NIR) emission without toxicity in the dark. In addition, clinically used traditional PSs encounter quenched fluorescence and decreased 1O2 production because of molecular aggregation in aqueous solution. To solve the aforementioned issues, quinoxalinone CN (QCN) with effective 1O2 generation under long-wavelength (530 nm) laser irradiation and aggregation-induced NIR emission is rationally designed by precise optimization of the quinoxalinone scaffold. After being encapsulated by an amphiphilic polymer (DSPE-PEG), the yielded nanoparticles exhibit highly efficient 1O2 production and stable NIR fluorescence located at 800 nm without obvious toxicity under the dark. Both in vitro and in vivo evaluation identify that QCN would be a promising PS for image-guided PDT of tumors.

Nucleolus-Targeted Photodynamic Anticancer Therapy Using Renal-Clearable Carbon Dots.

Photodynamic therapy (PDT), which utilizes light excited photosensitizers (PSs) to generate reactive oxygen species (ROS) and consequently ablate cancer cells or diseased tissue, has attracted a great deal of attention in the last decades due to its unique advantages. In order to further enhance PDT effect, PSs are functionalized to target specific sub-cellular organelles, but most PSs cannot target nucleolus, which is demonstrated as a more efficient and ideal site for cancer treatment. Here, an effective carbon dots (C-dots) photosensitizer with intrinsic nucleolus-targeting capability, for the first time, is synthesized, characterized, and employed for in vitro and in vivo image-guided photodynamic anticancer therapy with enhanced treatment performance at a low dose of PS and light irradiation. The C-dots possess high ROS generation efficiency and fluorescence quantum yield, excellent in vitro and in vivo biocompatibility, and rapid renal clearance, endowing it with a great potential for future translational research.

Tumor Microenvironment Targeting Nano-Bio Emulsion for Synergistic Combinational X-Ray PDT with Oncolytic Bacteria Therapy.

Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano-bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF4 :Tb,Ce@NaGdF4 core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano-bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano-bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T1 -weighted magnetic resonance imaging. Following the image-guided X-ray PDT and anaerobic C. novyi- NT combination treatment, apoptotic cell death in cancer tissues, including both peripheral and central tumor regions, is significantly higher than in the control groups. This combination therapy approach using a nano-bio therapeutic emulsion is expected to overcome the limitations of conventional cancer therapy, resulting in increased cancer-therapeutic efficacy.

Enzyme‐Triggered Disassembly of Perylene Monoimide‐based Nanoclusters for Activatable and Deep Photodynamic Therapy

Photodynamic therapy (PDT) exhibits great potential for cancer therapy, but still suffers from nonspecific photosensitivity and poor penetration of photosensitizer. Herein, a smart perylene monoimide-based nanocluster capable of enzyme-triggered disassembly is reported as an activatable and deeply penetrable photosensitizer. A novel carboxylesterase (CE)-responsive tetrachloroperylene monoimide (P1) was synthesized and assembled with folate-decorated albumins into a nanocluster (FHP) with a diameter of circa 100 nm. Once P1 is hydrolyzed by the tumor-specific CE, FHP disassembles into ultrasmall nanoparticles (ca. 10 nm), facilitating the deep tumor penetration of FHP. Furthermore, such enzyme-triggered disassembly of FHP leads to enhanced fluorescence intensity (ca. 8-fold) and elevated singlet oxygen generation ability (ca. 4-fold), enabling in situ near-infrared fluorescence imaging and promoted PDT. FHP permits remarkable tumor inhibition in vivo with minimal side effects through imaging-guided, activatable, and deep PDT. This work confirms that this cascaded multifunctional control through enzyme-triggered molecular disassembly is an effective strategy for precise cancer theranostics.

Platinum(II) ring-fused chlorins as efficient theranostic agents: Dyes for tumor-imaging and photodynamic therapy of cancer

The discovery of Pt-chlorin-type theranostic agents is described. Luminescent Pt(II) 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins, with different degrees of hydrophilicity, have been synthesized and their in vitro photocytotoxicity against human melanoma, oesophageal and bladder carcinomas was studied. A di(hydroxymethyl)-substituted chlorin was identified as a privileged molecule to explore imaging-guided photodynamic therapy. In addition to the high activity as PDT agent and absence of cytotoxicity per se, this molecule showed the ideal photophysical and photochemical properties. In vivo studies using a A375 melanoma mouse model, proved the extraordinary properties of this chlorin as a luminescent probe and the ability to impair tumor growth, making image guided treatment and follow up a possibility.

Amylase-Protected Ag Nanodots for in vivo Fluorescence Imaging and Photodynamic Therapy of Tumors.

BackgroundFluorescent metallic nanodots (NDs) have become a promising nanoprobe for a wide range of biomedical applications. Because Ag NDs have a high tendency to be oxidized, their synthesis and storage are a big challenge. Thus, the method for preparing stable Ag NDs is urgently needed. Surface modification and functionalization can enrich the capability of Ag NDs.MethodsIn this work, fluorescent Ag NDs were synthesized in deoxygenated water by using porcine pancreatic α-amylase (PPA) as the stabilizing/capping agent. The absorption and fluorescence of PPA-protected Ag NDs (PPA@AgNDs) were measured with a spectrophotometer and a spectrofluorometer, respectively. The morphology of PPA@AgNDs was characterized by high-angle annular dark-field (HAADF) scanning transmission electron microscopy (STEM). The biocompatibility of PPA@AgNDs was evaluated by tetrazolium (MTT)-based assay. PolyLys-Cys-SH (sequence: KKKKKKC) peptides were conjugated to PPA@AgNDs via heterobifunctional crosslinkers. PolyLys-Cys-linked PPA@AgNDs absorbed 5-aminolevulinic acid (ALA) by electrostatic interaction at physiological pH. The capability of tumor targeting was evaluated by intravenously injecting PPA@AgND-ALA into 4T1 breast cancer xenograft mouse models. Photodynamic therapy (PDT) against tumors was performed under 635 nm laser irradiation.ResultsPPA@AgNDs emitted at 640 nm with quantum yield of 2.1%. The Ag NDs exhibited strong photostability over a long period and a fluorescence lifetime of 5.1 ns. PPA@AgNDs easily entered the cells to stain the nuclei, showing the capabilities of living cell imaging with negligible cytotoxicity. ALA-loaded PPA@AgNDs (PPA@AgND-ALA) presented the superiority of passive tumor targeting via the enhanced permeability and retention (EPR) effect. Tumors were visualized in the near-infrared (NIR) region with reduced background noise. ALA molecules released from PPA@AgND-ALA was converted into the photosensitizer (PS) of protoporphyrin IX (PpIX) intracellularly and intratumorally, which greatly improved the PDT efficacy.ConclusionOur approach opens a new way to design a novel theranostic nanoplatform of PPA@AgND-ALA for effective tumor targeting and fluorescence image-guided PDT.

Theranostic Nanoparticles with Aggregation-Induced Emission and MRI Contrast Enhancement Characteristics as a Dual-Modal Imaging Platform for Image-Guided Tumor Photodynamic Therapy.

IntroductionAdvanced tumor-targeted theranostic nanoparticles play a key role in tumor diagnosis and treatment research. In this study, we developed a multifunctional theranostic platform based on an amphiphilic hyaluronan/poly-(N-ε-carbobenzyloxy-L-lysine) derivative (HA-g-PZLL), superparamagnetic iron oxide (SPIO) and aggregation-induced emission (AIE) nanoparticles for tumor-targeted magnetic resonance (MR) and fluorescence (FL) dual-modal image-guided photodynamic therapy (PDT).Materials and MethodsThe amphiphilic hyaluronan acid (HA) derivative HA-g-PZLL was synthesized by grafting hydrophobic poly-(N-ε-carbobenzyloxy-L-lysine) (PZLL) blocks onto hyaluronic acid by a click conjugation reaction. The obtained HA-g-PZLLs self-assembled into nanoparticles in the presence of AIE molecules and SPIO nanoparticles to produce tumor-targeted theranostic nanoparticles (SPIO/AIE@HA-g-PZLLs) with MR/FL dual-modal imaging ability. Cellular uptake of the theranostic nanoparticles was traced by confocal laser scanning microscopy (CLSM), flow cytometry and Prussian blue staining. The intracellular reactive oxygen species (ROS) generation characteristics of the theranostic nanoparticles were evaluated with CLSM and flow cytometry. The effect of PDT was evaluated by cytotoxicity assay. The dual-mode imaging ability of the nanoparticles was evaluated by a real-time near-infrared fluorescence imaging system and magnetic resonance imaging scanning.ResultsThe resulting theranostic nanoparticles not only emit red fluorescence for high-quality intracellular tracing but also effectively produce singlet oxygen for photodynamic tumor therapy. In vitro cytotoxicity experiments showed that these theranostic nanoparticles can be efficiently taken up and are mainly present in the cytoplasm of HepG2 cells. After internalization, these theranostic nanoparticles showed serious cytotoxicity to the growth of HepG2 cells after white light irradiation.DiscussionThis work provides a simple method for the preparation of theranostic nanoparticles with AIE characteristics and MR contrast enhancement, and serves as a dual-modal imaging platform for image-guided tumor PDT.

Molecular Design of Highly Efficient Heavy-Atom-Free Triplet BODIPY Derivatives for Photodynamic Therapy and Bioimaging.

Novel BODIPY photosensitizers were developed for imaging-guided photodynamic therapy. The introduction of a strong electron donor to the BODIPY core through a phenyl linker combined with the twisted arrangement between the donor and the BODIPY acceptor is essential for reducing the energy gap between the lowest singlet excited state and the lowest triplet state (ΔEST ), leading to a significant enhancement in the intersystem crossing (ISC) of the BODIPYs. Remarkably, the BDP-5 with the smallest ΔEST (ca. 0.44 eV) exhibited excellent singlet oxygen generation capabilities in both organic and aqueous solutions. BDP-5 also displayed bright emission in the far-red/near-infrared region in the condensed states. More importantly, both in vitro and in vivo studies demonstrated that BDP-5 NPs displayed a high potential for photodynamic cancer therapy and bioimaging.

An 808 nm Light-Sensitized Upconversion Nanoplatform for Multimodal Imaging and Efficient Cancer Therapy.

Photodynamic therapy (PDT) is commonly employed in clinics to treat the cancer, but because of the hypoxic tumor microenvironment prevalent inside tumors, PDT therapeutic efficiency is not adequate hence limiting the effectiveness of PDT. Therefore, we designed a nanocomposite consisting of reduced nanographene oxide (rGO) modified with polyethylene glycol (PEG), manganese dioxide (MnO2), upconversion nanoparticles (UCNPs), and Chlorin e6 (Ce6) to spark oxygen production from H2O2 with the aim of relieving the tumor hypoxic microenvironments. For in vivo tumor PDT and photothermal therapy (PTT), UCNPs-Ce6-labeled rGO-MnO2-PEG nanocomposites were used as a therapeutic agent, augmenting the therapeutic efficiency of PDT via redox progression through the catalytic H2O2 decomposition pathway and further achieving excellent tumor inhibition. It is important to mention that degradation of MnO2 in an acidic cellular microenvironment leads to the creation of a massive volume of Mn2+ which was employed as a contrast mediator for magnetic resonance imaging (MRI). Our research postulates an approach to spark O2 formation through an internal stimulus to augment the efficiency of MRI- and computerized tomography (CT)-imaging-guided PDT and PTT.

Mutual impact of clinically translatable near-infrared dyes on photoacoustic image contrast and in vitro photodynamic therapy efficacy.

.Photodynamic therapy (PDT), a spatially localized phototoxic therapy that involves irradiation of a photosensitizer (PS) with specific wavelengths of light, has shown exceptional promise in impacting cancer treatment outcomes, particularly oral cancer. To reduce PDT outcome variability, attempts toward image-guided personalized PDT are being pursued by monitoring PS uptake either via fluorescence or photoacoustic imaging (PAI), a nonionizing modality dependent on optical absorption properties of the tissue. PAI-guided PDT requires a near-infrared contrast agent for deep tissue imaging with minimal photobleaching effect. We evaluate the impact of PDT agent, benzoporphyrin derivative (BPD), on PAI agent indocyanine green (ICG) and vice versa, given that they have different optical absorption properties and singlet oxygen quantum yields for PDT. Specifically, we demonstrate in two oral squamous cell carcinoma lines (FaDu and SCC4) that ICG has minimal effect on BPD PDT efficacy when irradiated with either a continuous or pulsed laser. Furthermore, the impact of BPD on ICG photodegradation was monitored with PAI in tissue-mimicking phantoms. These studies inform us that the combination of BPD and ICG can be utilized for PAI-guided PDT. However, researchers need to consider the photodegradation effects of ICG in the presence of BPD when designing their drug delivery strategies for PAI-guided PDT.