Cancer development is related to genetic mutations in primary cells, where 5-10% of all cancers are derived from acquired genetic defects, most of which are a consequence of the environment and lifestyle. As it turns out, over half of cancer deaths are due to the generation of drug resistance. The local delivery of chemotherapeutic drugs may reduce their toxicity by increasing their therapeutic dose at targeted sites and by decreasing the plasma levels of circulating drugs. Nanobubbles have attracted much attention as an effective drug distribution system due to their non-invasiveness and targetability. This review aims to present the characteristics of nanobubble systems and their efficacy within the biomedical field with special emphasis on cancer treatment. In vivo and in vitro studies on cancer confirm nanobubbles\' ability and good blood capillary perfusion; however, there is a need to define their safety and side effects in clinical trials.

UNASSIGNED: Hematoporphyrin monomethyl ether (HMME) is a promising photosensitizer for photodynamic therapy (PDT) and has found wide application in the treatment of port-wine stains (PWS).
UNASSIGNED: This study aims to observe and analyze the clinical efficacy and safety of HMME-PDT in the treatment of PWS patients. It also aims to evaluate the usefulness of color Doppler flow imaging (CDFI), an ultrasound technique for detecting blood flow in skin lesions, in assessing clinical efficacy.
UNASSIGNED: Thirty-three patients with PWS underwent HMME-PDT at our dermatology outpatient clinic between January 2019 and March 2020. Data on patient demographics, lesion location, lesion type (pink, purple, nodular thickening), treatment frequency, and pre- and post-treatment images were collected and retrospectively analyzed. CDFI was performed on three patients.
UNASSIGNED: All patients received intravenous HMME and underwent irradiation with 532 nm green LED light. Of these, 5 patients received 1 session of HMME-PDT, 14 received 2 sessions, 9 received 3 sessions and the remaining 5 patients received more than 3 sessions. Of the 33 patients, 9 were cured (27.27%), 10 showed improvement (30.30%), 11 experienced a reduction in symptoms (33.33%), and 3 showed no significant improvement (9.09%). Most patients reported local pain and oedema, and no systemic adverse effects were observed. Clinical efficacy correlated with lesion type and total number of treatment sessions. CDFI appears to be an excellent technique for assessing clinical efficacy.
UNASSIGNED: HMME-PDT is a safe and effective method for the treatment of PWS. CDFI examination appears to be a promising assessment tool. However, further validation with larger sample sizes is warranted.

Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the \"gold standard\" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades.
To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities.
PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality.
A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults.
PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

BACKGROUND: Hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) has emerged as an alternative approach for port-wine stain (PWS), which was primarily treated with pulsed dye laser (PDL). This study was aimed to evaluate the efficacy and safety of HMME-PDT for PWS and to explore influential factors on the efficacy.
METHODS: A total of 254 patients were enrolled. Patients received an intravenous injection of HMME at 5 mg/kg. Lesion areas were irradiated with 532-nm light for 20-25 min. Efficacy was assessed according to fading of lesions and graded as excellent (≥90 %), good (60 %-89 %), fair (20 %-59 %), or poor (<20 %). Adverse events were recorded. Clinical data were analyzed including gender, age, lesion sub-type, lesion location and number of treatments.
RESULTS: Overall, 72.4 % of patients achieved an effective response, with 27.6% showing excellent efficacy, 24.8 % showing good efficacy and 20.1 % showing fair efficacy. Only 27.6 % showed poor efficacy. Patients under the age of 18 obtained a better efficacy than adults. Lesions in face showed a better therapeutic outcome than those in neck or trunk and extremities. A more effective response was seen in pink type compared with nodular thickening type. Multiple HMME-PDT treatments could improve the clinical response. Lesion location, lesion sub-type, number of treatments were independent influential factors on efficacy. Adverse events included edema, blister, crust, hypopigmentation, hyperpigmentation, pain, itch and burning sensation. No severe systemic side events were observed.
CONCLUSIONS: HMME-PDT was effective for treating PWS and was safe and well-tolerated by patients. It is worth further investigation in efficacy and safety involving more patients from medical institutions in different regions in China. The optimal treatment parameters and treatment protocols are still being explored in the clinical treatment for PWS.

BACKGROUND: Pulsed dye laser (PDL) is currently considered to be the first-line treatment for port-wine stains (PWSs) on the extremities despite its less than satisfactory therapeutic efficacy. Hemoporfin-mediated photodynamic therapy (HMME-PDT) is a vascular-targeted therapy that has rarely been used to treat PWSs on the extremities. Here, we evaluate the clinical efficacy and safety of HMME-PDT for the treatment of PWSs on the extremities.
METHODS: Clinical data and dermoscopic images of PWSs on the extremities were obtained from 65 patients who underwent HMME-PDT between February 2019 and December 2022. The clinical efficacy of HMME-PDT was analyzed by comparing the pre- and post-treatment images. The safety of HMME-PDT was evaluated through observation during the treatment period and post-treatment follow-up.
RESULTS: The efficacy rate of a single HMME-PDT session was 63.0% and that of two and three to six sessions was 86.7% and 91.3%, respectively. A positive correlation was found between therapeutic efficacy and the number of HMME-PDT sessions. The therapeutic efficacy of HMME-PDT was better on the proximal extremities than on other parts of the extremities (P = 0.038), and the efficacy of treating PWSs in each site was relatively improved with an increase of treatment time. The clinical efficacy of HMME-PDT differed across four PWS vascular patterns identified by dermoscopy (P = 0.019). However, there was no statistical difference in the therapeutic efficacy based on age, sex, type of PWS, and treatment history (P > 0.05), which may be partly attributed to the relatively small sample size or poor cooperation of infant patients. No obvious adverse reactions were observed during the follow-up period.
CONCLUSIONS: HMME-PDT is a very safe and effective treatment for PWSs on the extremities. Multiple HMME-PDT treatments, lesions located in proximal limbs, and PWSs with type I and IV vascular patterns under dermoscopy were associated with higher efficacy of HMME-PDT. Dermoscopy may help predict the clinical efficacy of HMME-PDT.
BACKGROUND: 2020KJT085.

Port-wine birthmark (PWB) are congenital vascular malformations that commonly occur on the face and neck, with an incidence of 0.3-0.5% in the general population, causing significant negative psychological effects and economic burden to patients. Nevertheless, amidst the plethora of different treatment methods for PWB, choosing the option that best suits the patient\'s need can be a challenge. In recent years, traditional treatment methods for PWB have been replaced by new therapies, and radioactive nuclide patch therapy is one of them. A panel of experts sought to describe herein 4 clinical cases, illustrating the PDT can demonstrate good precision and efficacy in the treatment of PWB. The research findings show the 4 patients in this group had a history of treatment with radioactive isotope patches. After 2-3 sessions of HMME-PDT, all cases achieved satisfactory results, the color of the red skin lesions significantly faded, and the area of the lesions decreased noticeably. Superficial tissue ultrasound showed a reduction in lesion thickness before and after treatment. In summary, for cases where the efficacy of PWB treatment with radioactive isotope patches is inadequate, Photodynamic therapy (PDT) can be used as a treatment reference.

The objective of this study was to determine the mechanism and effect of hematoporphyrin monomethyl ether mediated photodynamic therapy (HMME-PDT) on oral squamous cell carcinoma (OSCC). Human OSCC CAL-27 cells were randomly divided into four groups: control group, HMME group, laser group, and HMME-PDT group. Cell viability was detected by the CCK-8 method. Cell cycle distribution was evaluated by flow cytometry. GEO database was used to screen differentially expressed microRNAs (DEMs), and TCGA database was performed to verify DEM expression in OSCC and normal tissues. The effects of HMME-PDT on DEM expression were assayed by real-time PCR, and the expressions of miRNAs target genes were measured by western blot. Fluorescence probes were used to determine the production of singlet oxygen (1O2). Compared with the other three groups, HMME-PDT dramatically inhibited CAL-27 cell proliferation and induced G0/G1 cycle arrest. The expressions of miR-21 and miR-155 were significantly upregulated in OSCC. HMME-PDT downregulated the expression of miR-21 but had no obvious effect on miR-155. HMME-PDT remarkably upregulated the levels of P53 and miR-21 target proteins, such as PDCD4, RECK, and SPRY2. 1O2 was generated during HMME-PDT, and inhibition of 1O2 production could reverse the regulation of HMME-PDT on P53, miR-21, and its target proteins, thus restoring cell viability. HMME-PDT can significantly inhibit the growth of OSCC cells, and the mechanism of this effect is related to the regulation of the P53-miR-21-PDCD4 axis via 1O2 induced by HMME-PDT.

BACKGROUND: Hematoporphyrin monomethyl ether-photodynamic therapy (HMME-PDT) has been showing promising results in the treatment of port-wine stains (PWSs). We evaluated the clinical efficacy and treatment response of HMME-PDT in adult Chinese patients with PWSs.
METHODS: A single-center retrospective study recruited adult PWS patients with negative HMME skin test results from December 2017 to May 2020. Patients received an intravenous injection of 5 mg/kg HMME and the lesions were exposed to 532 nm LED green light with an irradiation power density of 85-95 mW/cm2 for 20-25 min. Digital photographs were taken before and after two therapy sessions and observed by three blinded dermatologists for clinical response.
RESULTS: A total of 72 patients aged between 18 and 55 years were recruited. There were 65 patients of the flat purple type, 5 of the hypertrophic type, and 2 of the nodular thickening type. Of the 65 patients, 7 showed excellent efficacy (10.77%), 13 patients indicated good efficacy (20.00%), 47 patients showed fair efficacy (64.62%), while 3 cases displayed no improvement (4.62%). All five patients of the purple and hypertrophic type showed fair efficacy (100%), and no improvement was observed in patients of the nodular thickening type (100%). Pain, pruritus, and a burning sensation were observed during treatment. Edema was noted on the treated areas post-treatment. No other obvious systemic adverse reactions were observed.
CONCLUSIONS: HMME-PDT is an effective and safe treatment for adult patients with purple PWSs. Multiple HMME-PDT treatments can improve the response and cure rate.

Nevus flammeus (NF) is a congenital vascular malformation.
To investigate the acute effect of a variable pulse width Nd:YAG laser combined with hematoporphyrin monomethyl ether (HMME)-mediated photodynamic therapy (PDT) on a cockscomb model of NF.
Forty-two leghorn roosters were randomly divided into the following 7 groups: group A1 (treated with HMME-mediated PDT; energy density of 75 J/cm2), group A2 (treated with HMME-mediated PDT; 125 J/cm2), group A3 (treated with HMME-mediated PDT; 150 J/cm2), group A4 (treated with HMME-mediated PDT; 175 J/cm2), group B (treated with a variable pulse width Nd:YAG laser), group C (treated with a variable pulse width Nd:YAG laser and HMME-mediated PDT), and group D (the control group). Changes in the cockscomb tissues were observed visually and microscopically on days 1, 3, 7, and 14 after treatment. The capillary reduction and the ratio of collagen type I to type III were examined.
The response rate was higher in groups A3 and A4 than in group B. In group A, a higher energy density resulted in a higher response rate and a greater capillary reduction (p < 0.05 for all). However, we concluded that PDT at an energy density of 175 J/cm2 is not suitable for treating NF, as severe tissue damage, markedly lower capillary numbers, and markedly higher collagen type I:III ratios were observed in the cockscombs treated at this energy density; instead, 150 J/cm2 may be a more appropriate energy density. Moreover, HMME-mediated PDT at 150 J/cm2 combined with a variable pulse width Nd:YAG laser achieved better treatment outcomes than PDT or a variable pulse width Nd:YAG laser alone (p < 0.05 for both).
Compared to PDT or a variable pulse width Nd:YAG laser alone, the combination of the 2 therapies achieved a better acute effect in treating a cockscomb model of NF, and 150 J/cm2 may be a suitable energy density for PDT.

Treating hypertrophic scars is a challenge for clinicians. Herein, we report a case of one female with both a facial port wine stain and a hypertrophic scar treated with Hematoporphyrin monomethyl ether photodynamic therapy. Surprisingly, with the treatment of the facial port wine stain, the other skin lesion, the hypertrophic scar, also alleviated. HMME-PDT has been approved for application in PWS; however, this case showed effective easing of the hypertrophic scar lesion, which indicates that it might be a promising therapeutic method for hypertrophic scars.