Hypocrellin B Research Articles

A glutathione responsive photosensitizer based on hypocrellin B for photodynamic therapy

As a typical natural photosensitizer, hypocrellin B (HB) offers the advantages of high molar extinction coefficient, high phototoxicity, low dark toxicity, and fast metabolism in vivo. However, the lack of tumor specificity hinders its clinical applications. Herein, we designed and synthesized a glutathione (GSH) responsive photosensitizer based on HB. The 7 − nitro − 2,1,3 − benzoxadiazole (NBD) covalently connected to HB not only served as a fluorescence quenching group but also as a GSH activating group. The photosensitizer HB−NBD showed almost no fluorescence and singlet oxygen generation as a result of the photoinduced electron transfer between HB and NBD. The designed photosensitizer HB−NBD can be activated by GSH in solutions and cancer cells, and then obtain recuperative fluorescence and photosensitive activity.

Chemo-photodynamic antitumour therapy based on Er-doped upconversion nanoparticles coated with hypocrellin B and MnO2

An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.

Upconversion luminescence nanosensor for detection of Fe3+ and phosphate ion based on the inner-filter effect.

In this work, an upconversion luminescence (UCL) nanosensor for fast detection of ferric ion (Fe3+) and phosphate ion (Pi) is developed based on the inner-filter effect (IFE) between NaYF4:Yb/Er upconversion nanoparticles (UCNPs) and Fe3+-hypocrellin B (HB) complex. Fe3+-HB complex has strong absorption band (450-650nm), which overlaps with the green emission peak of UCNPs at 545nm. By adding Fe3+ and Pi, the UCNPs-HB system produces the red-shift change of absorption spectrum, which leads to the "on-off-on" process of IFE. So, with the specific recognition ability of HB for Fe3+ and the competitive complexation of Pi for Fe3+, the proposed nanosensor utilizes the UCL change to achieve the detection of the targets. For the detections of Fe3+, the linear range is 10-600μM with a limit of detection (LOD) of 2.62μM, and for Pi, the linear range is 5-100μM with a LOD of 1.25μM. The results for selectivity, precision, and recovery test are also satisfactory. Furthermore, the real sample detection shows that the proposed nanaosensor has a great potential in environmental and biological systems. An upconversion luminescence (UCL) nanosensor based on the inner-filter effect (IFE) between upconversion nanoparticles (UCNPs) and Fe3+-hypocrellin B (HB) complex for the detection of Fe3+ and phosphate ion has been proposed, which is promising to be a convenient and sensitive assay for monitoring Fe3+ and phosphate ion in different environments and biological systems.

Supramolecular photosensitizers using extended macrocyclic hosts for photodynamic therapy with distinct cellular delivery.

The photosensitizers (PSs) for photodynamic therapy (PDT) mostly possess conjugated skeletons that are over-sized and poorly water-soluble to be encapsulated by conventional macrocyclic receptors. Herein, we report that two fluorescent hydrophilic cyclophanes, AnBox·4Cl and ExAnBox·4Cl, can effectively bind hypocrellin B (HB), a pharmaceutically active natural PS for PDT, with binding constants of the 107 level in aqueous solutions. The two macrocycles feature extended electron-deficient cavities and can be facilely synthesized through photo-induced ring expansions. The corresponding supramolecular PSs (HB⊂AnBox4+ and HB⊂ExAnBox4+) exhibit desirable stability, biocompatibility, and cellular delivery, as well as excellent PDT efficiency against cancer cells. In addition, living cell imaging results indicate that HB⊂AnBox4+ and HB⊂ExAnBox4+ have different delivery effects at the cellular level.

Photodynamic inactivation of Staphylococcus aureus in the system of titanium dioxide nanoparticles sensitized by hypocrellin B and its application in food preservation

Staphylococcus aureus (S. aureus) is a foodborne pathogen that endangers human health worldwide. Antimicrobial photodynamic inactivation (aPDI), mediated by titanium dioxide nanoparticles (TiO2NP), was recently used to control the growth of S. aureus, however, UV illumination had to be offered to initiate the photodynamic reaction. To overcome this drawback, a dual-photon system was established here based on TiO2NP and hypocrellin B (HB), a natural pigment with photocatalyst activity. Irradiated at the visible light (9 J/cm2) at the wavelength of 460 nm, the joint use of both photosensitizers (PS) caused a substantial decline of staphylococcal survival, reaching a maximum decrease of 4 ∼ 5 logs. When 10 nM HB and 100 µM TiO2NP were applied, a synergistic photokilling effect was achieved, only in the mixed phase of anatase/rutile, Degussa P25. Regarding the antimicrobial mechanisms, it was found that the membrane integrity of S. aureus was heavily disrupted, surface morphology was altered, intracellular substances like potassium and DNA were leaked, and biofilm formation was significantly circumvented due to the excitation of sensitized PS. In terms of antioxidant responsiveness of S. aureus, qPCR results showed that a series of genes encoding the membrane-associated cell death effectors were deregulated. Among them, LrgA was recognized as a key responsive element, due that the mutant strain harboring a constitutively-expressed LrgA strengthened the bactericidal effect of aPDI. Finally, the dual-photon strategy lowered the microbial contamination in the tested apple with its quality maintained, under the condition of visible light. Taken together, a new dual-photon system based on TiO2NP and HB was constructed and validated in photokilling S. aureus, providing a well-adapted technique to maintain food safety.

Ultrasound-Enhanced Self-Exciting Photodynamic Therapy Based on Hypocrellin B.

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment.

Synergistic effect of hypocrellin B and curcumin on photodynamic inactivation of Staphylococcus aureus.

Antimicrobial photodynamic inactivation (aPDI) serves as a new approach to control the growth of foodborne bacteria. It remains elusive if the photodynamic efficacy of hypocrellin B (HB) can be potentiated by joint action with curcumin. In this study, we measured the survival rate of Staphylococcus aureus strains under the varying photodynamic conditions. According to our data, a maximum of 5-6 log10 decrease of bacterial survival can be achieved under the tested conditions (500nM, 9Jcm-2 ). Regarding the bactericidal mechanisms, HB-based aPDI disrupted the membrane integrity of staphylococcal cells, probably owing to the stimulated reactive oxygen species (ROS). In addition, aPDI disrupted the enzymatic activities of bacterial antioxidant proteins and caused the leakage of multiple intracellular substances. The HB-mediated photodynamic efficacy was potentiated by the addition of curcumin with a sublethal dose. This dual-photon synergy arose from unique aPDI conditions (100nM each and 9Jcm-2 ). The synergistic action might be accounted for by the increased type I/type II ratio of ROS, as evidenced by the effect of different quenchers. Finally, the joint use of photosensitizers reduced the microbial contamination of the tested apple while maintaining its quality. In summary, photodynamic inactivation based on dual photons showed synergistic activity in controlling the growth of Staphylococcal aureus, which provided a novel approach to maintain food safety.

Near-Infrared Hypocrellin Derivatives for Synergistic Photodynamic and Photothermal Therapy.

Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600-900 nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near-infrared (NIR) region, NIR emission (peaked at 805 nm), and singlet oxygen quantum yields of 0.27/0.31. HE-PEG-NPs were also prepared using 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE-PEG-NPs not only retained their 1 O2 -generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and in vivo therapeutic results revealed that the synergetic effect of HE-PEG-NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE-PEG-NPs could be regarded as a promising phototheranostic agent.

Hypocrellin B triggered sonodynamic therapy reverses multidrug resistance of doxorubicin-resistant SGC7901/ADR cells via down-regulation of P-gp expression

The combating of multidrug resistance (MDR) plays a crucial role in effective chemotherapy. However, current strategies for cancer of MDR remain unsatisfactory for their limited efficacy and severe side effects. In this study, we sought to determine the anti-MDR effects of a traditional chinese herb, Hypocrellin B (HB)-mediated sonodynamic therapy (HB-SDT) on human gastric multidrug resistance cancer SGC-7901cell/ADR cells and its underlying mechanisms. HB-SDT can synergistically increase the cytotoxicity of DOX on SGC-7901cell/ADR cells in which the mechanism is related to significant promotion of apoptosis, ROS level and drop of MMP in the resistant cells after combining treatment of DOX and HB-SDT. Meanwhile, western blotting assays display the expression of apoptosis related proteins Bax and Bcl-2 changed markedly after the combination treatment. In addition, the expression of P-gp was significantly down-regulated after treatment of HB-SDT and DOX. HB-SDT can increase DOX-induced mitochondrial-dependent apoptosis by inhibiting the expression of P-gp, thereby increasing the cytotoxic effect into SGC7901/ADR cells.

In vitro photodynamic inactivation effects of hypocrellin B on azole-sensitive and resistant Candida albicans.

The extensive use of antifungal drugs has led to resistance from Candida albicans. The search for alternative treatment against drug-resistant C. albicans is highly desirable. Antimicrobial photodynamic therapy (aPDT) is an emerging and promising approach for treating localized and superficial C. albicans infections. The aim of this study was to investigate the photodynamic inactivation (PDI) effects of hypocrellin B (HB) on azole-sensitive and resistant C. albicans in vitro. The PDI efficacies of HB on standard C. albicans strain (ATCC 10231), azole-sensitive clinical isolate of C. albicans, and azole-resistant clinical isolate of C. albicans were assessed. The uptake of HB in C. albicans cells was investigated by confocal laser scanning microscopy (CLSM). The PDI effects on cellular structure and surface characteristics were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). HB exhibited no significant dark toxicity, but inactivated the azole-sensitive and resistant C. albicans in a light-dose and PS concentration-dependent manner. CLSM images indicated that PDI treated C. albicans cells showed stronger fluorescence compared to untreated cells. TEM images suggested that significant damage to the cell wall, membrane, and cytoplasm were induced by HB-mediated PDI. SEM analysis revealed that the surface of C. albicans cells became twisted and ruptured after PDI treatment. Azole-sensitive and resistant C. albicans could be effectively inactivated by HB in the presence of light, and HB-mediated aPDT shows promise as an antifungal treatment for C. albicans.

Biodegradable hypocrellin derivative nanovesicle as a near-infrared light-driven theranostic for dually photoactive cancer imaging and therapy

Photoactive agents based on natural products have attracted substantial attention in clinical applications because of their distinct biological activity, molecular structure multiformity, and low biotoxicity. Herein, we initially modify hypocrellin B (HB) with 1,2-diamino-2-methyl propane to form near-infrared (NIR) light (>700 nm)-responsive amino-substituted HB derivative (DPAHB). The DPAHB exhibit broad absorption (400–800 nm), NIR emission (maximum emission peak at 710 nm), and high singlet oxygen (1O2) quantum yield (∼0.33) under NIR light (721 nm) irradiation. After self-assembly by using DPAHB with PEG-PLGA, the as-prepared nanovesicles (DPAHB NVs) retain efficient 1O2 generation, more interestingly, show high photothermal conversion efficiency (∼0.24) under NIR light (721 nm) irradiation for synergistic photodynamic therapy (PDT) and photothermal therapy toward hypoxic tumor. The DPAHB NVs can not only be as a fluorescence/photoacoustic imaging agent but also exhibit an even stronger PDT efficiency than that of chlorin e6 (a widely used classic photosensitizer). In vitro and in vivo studies demonstrate that DPAHB NVs possess high photothermal stability, enhanced tumor accumulation, and suitable biodegradation rate, thus, show a highly promising clinical potential as a new photoactive agent for cancer therapy.

Design of an Amphiphilic iRGD Peptide and Self-Assembling Nanovesicles for Improving Tumor Accumulation and Penetration and the Photodynamic Efficacy of the Photosensitizer

Photodynamic therapy (PDT) is a minimally invasive treatment for many diseases, including infections and tumors. Nevertheless, clinical utilization of PDT is severely restricted due to the shortcomings of the photosensitizers, especially their low water solubility and poor tumor selectivity. iRGD (internalizing RGD, CRGDKGPDC), a nine-unit cyclic peptide, was applied as an active ligand to realize tumor homing and tissue penetration. Herein, we innovatively fabricated a novel OFF-ON mode iRGD-based peptide amphiphile (PA) to self-assemble into spherical nanovesicles to enhance the tumor-targeting and tumor-penetrating efficacy of PDT. To introduce the self-assembling feature into iRGD, a hydrophilic arginine-rich sequence and hydrophobic alkyl chains were sequentially linked to the iRGD motif. A short proline sequence was selected to control the morphology of the self-assembled aggregates. Next, the photosensitizer hypocrellin B (HB) was encapsulated into PA vesicles with a high loading efficiency. The aggregation-caused quenching effect inactivated HB in the PA vesicles; however, the iRGD-peptide-based material was able to be selectively degraded in tumor cells. Thus, the HB fluorescence was recovered to achieve tumor-targeted imaging. This approach endows HB-loaded PA vesicles (HB-PA) with tumor-targeted activation, preferable tumor accumulation, and deep tumor penetration, thus leading to an excellent fluorescence-imaging-guided photodynamic efficacy both in vitro and in vivo. These amphiphilic iRGD aggregates provide a novel strategy for improving the accumulation, penetration, and imaging-guided photodynamic efficacy of photosensitizers.

Hypocrellin B-loaded, folate-conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer invitro and invivo.

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)‐poly (lactic acid)(PLA)‐folate (FA‐PEG‐PLA) was prepared in order to synthesize an active‐targeting, water‐soluble and pharmacomodulated photosensitizer nanocarrier. Drug‐loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA‐PEG‐PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA‐PEG‐PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA‐PEG‐PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR−). The enhanced uptake of HB/FA‐PEG‐PLA micelles to cancer cells resulted in a more effective post‐PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA‐PEG‐PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate‐targeted micelles in tumor‐bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20‐fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB‐loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA‐PEG‐PLA micelles have a high drug‐loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy.

Targeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)-induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)-loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC-cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF-assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.

Magnetic Mesoporous Silica Nanoparticles Cloaked by Red Blood Cell Membranes: Applications in Cancer Therapy

AbstractTargeted drug delivery is an emerging technological strategy that enables nanoparticle systems to be responsive for tumor therapy. Magnetic mesoporous silica nanoparticles (MMSNs) were cloaked with red blood cell membrane (RBC). This integrates long circulation, photosensitizer delivery, and magnetic targeting for cancer therapy. In vivo experiments demonstrate that RBC@MMSNs can avoid immune clearance and achieve magnetic field (MF)‐induced high accumulation in a tumor. When light irradiation is applied, singlet oxygen rapidly generates from hypocrellin B (HB)‐loaded RBC@MMSN and leads to the necrosis of tumor tissue. Such a RBC‐cloaked magnetic nanocarrier effectively integrates immunological adjuvant, photosensitizer delivery, MF‐assisted targeting photodynamic therapy, which provides an innovative strategy for cancer therapy.

Development of copolymeric nanoparticles of hypocrellin B: Enhanced phototoxic effect and ocular distribution

In the present work, we have developed a photosensitizer hypocrellin B (HB) and nano silver loaded PLGA-TPGS nanoparticles with improved singlet oxygen production for enhanced photodynamic effect for the efficient treatment of age related macular degeneration. Random copolymer (PLGA-TPGS) synthesized by ring opening and bulk polymerization was characterized by IR, 1H NMR and TGA analysis. HBS-CP-NPs prepared by nanoprecipitation techniques were spherical shaped 89.6–753.6nm size particles with negative zeta potential. The average encapsulation efficiency was 84.06±11.43% and HB release from the HBS-CP-NPs was found to be biphasic with a slow release of 1.41% in the first 8h and 48.91% during 3days as measured by RP-HPLC. DSC thermograms indicate that HB was dispersed as amorphous form in HBS-CP-NPs. The ROS generation level of HBS-CP-NPs was significantly higher than that of HB/HB-CP-NPs. The production of 1O2 of HBS-CP-NPs has been assessed using EPR spectrometer. The 1O2 generating efficiency follows the order of nano silver>HB-CP-NPs>HBS-CP-NPs>pure HB drug solution. The superior phototoxic effect of HBS-CP-NPs (85.5% at 50μM) was attained at 2h irradiation in A549 cells. Significant anti angiogenic effect of HBS-CP-NPs was observed in treated CAM embryos. Following intravenous injection of HBS-CP-NPs to rabbits, the maximum amount of HB was found in retina (3h), iris (9h), aqueous humour (9h) and vitreous humour (9h).

Hypocrellin B and nano silver loaded polymeric nanoparticles: Enhanced generation of singlet oxygen for improved photodynamic therapy

A nanoparticulate photodynamic approach was employed with an objective to achieve enhanced production of singlet oxygen (1O2), for the management of posterior segment eye diseases like age related macular degeneration. The hypocrellin B (HB) loaded poly lactide-co-glycolide nanoparticle formulations were incorporated with nano silver (HBS-NPs). The optimized HBS-NPs contained 2.60±0.06mg/mL of HB and showed (i) 135.6 to 828.2nm size range, and (ii) negative zeta potential with a narrow polydispersity index. The DSC thermograms suggested the amorphous nature of HB inside the HBS-NPs. With the average encapsulation efficiency of 92.9±1.79%, the drug release from the HBS-NPs followed a biphasic pattern with an initial burst of 3.50% during first 8h followed by a sustained release of 47.82% within 3days. The interaction between nano silver and HB as assessed by the increase in spectral intensity of Raman spectrum demonstrates that HB may be attached over the nano silver. Generation of reactive oxygen species (ROS) by HBS-NPs was significantly higher than that of HB/HB-NPs. The singlet oxygen generating efficiency assessed using EPR spectrometer follows the order of nano silver>HB-NPs>pure HB drug solution>HBS-NPs. The HBS-NPs had a concentration and time dependent phototoxicity on A549 (human adeno lung carcinoma) cells in the presence of light providing a superior phototoxic effect (82.2% at 50μM) at 2h irradiation. The CAM treated with HBS-NPs showed a significant anti-angiogenic effect compared to a blank formulation. In vivo biodistribution studies revealed that intravenous administration of HBS-NPs lead into significant exposure to the posterior segment of the eye. This proof of principle study demonstrates that HB based nanoparticles may be a valuable new tool for application in ocular photodynamic therapy for the treatment of AMD in future.

Effects of Photodynamic Therapy Using Yellow LED-light with Concomitant Hypocrellin B on Apoptotic Signaling in Keloid Fibroblasts

Keloid is a common and refractory disease characterized by abnormal fibroblast proliferation and excessive deposition of extracellular matrix components. Hypocrellin B (HB) is a natural perylene quinone photosensitizer. In this experiment, we studied the effects of photodynamic therapy (PDT) using yellow light from light-emitting diode (LED) combined with HB on keloid fibroblasts (KFB) in vitro. Our results showed that HB-LED PDT treatment induced significant KFB apoptosis and decreased KFB cell viability. HB-LED PDT treatment lead to significant BAX upregulation and BCL-2 downregulation in KFB cells, which led to elevation of intracellular free Ca2+ and activation of caspase-3. Our data provides preliminary evidence for the potential of HB-LED PDT as a therapeutic strategy for keloid.

Using porous CaCO3/hyaluronic acid nanocages to accommodate hydrophobic photosensitizer in aqueous media for photodynamic therapy

The solubility and stability of hydrophobic photosensitizer in aqueous solution have a great effect on the efficiency of Photodynamic Therapy (PDT) in cancer treatment. Herein, porous CaCO3 nanoparticles with a size about 250nm were prepared as a carrier for the photosensitizer Hypocrellin B (HB) to improve the encapsulation and delivery in aqueous solution. The encapsulation dosage of HB by porous CaCO3 nanoparticles was investigated and proved to be concentration dependent. After modified by cross-linked targeting molecule hyaluronic acid (HA), the hybrid nanoparticles were demonstrated the advantages for HB release by pH –sensitive structure and enhancement of PDT cytotoxicity to cancer cells. The hybrid nanoparticles obtained here are supposed to have a great potential application in the PDT.

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles.

Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light. To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied. CD44 is a well-known hyaluronic acid receptor that is often introduced as a biomarker of non-small cell lung cancer. In addition, a combination of PDT and chemotherapy is adopted in the present study. This combination concept may increase anticancer therapeutic effects and reduce adverse reactions. We chose hypocrellin B (HB) as a novel photosensitizer in this study. It has been reported that HB causes higher anticancer efficacy of PDT compared to hematoporphyrin derivatives1. Paclitaxel was selected as the anticancer drug since it has proven to be a potential treatment for lung cancer2. The antitumor efficacies of photosensitizer (HB) solution, photosensitizer encapsulated hyaluronic acid-ceramide nanoparticles (HB-NPs), and both photosensitizer- and anticancer agent (paclitaxel)-encapsulated hyaluronic acid-ceramide nanoparticles (HB-P-NPs) after PDT were compared both in vitro and in vivo. The in vitro phototoxicity in A549 (human lung adenocarcinoma) cells and the in vivo antitumor efficacy in A549 tumor-bearing mice were evaluated. The HB-P-NP treatment group showed the most effective anticancer effect after PDT. In conclusion, the HB-P-NPs prepared in the present study represent a potential and novel photosensitizer delivery system in treating lung cancer with PDT.