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Nanobodies have been extensively demonstrated in biomedical imaging and therapy. However, nanobody probes often suffer from rapid renal clearance due to its small size. Herein, we reported a recombinant nanobody with a 200 amino-acid polypeptide chain consisting of Pro, Ala, and Ser (PAS) at the C-terminal, which can be easily expressed in Escherichia coli with a high yield. The PASylated nanobody was functionalized with a fluorescent dye and the cell labeling properties were characterized by flow cytometry and confocal microscopy. In vivo fluorescence imaging indicated that the PASylated nanobody showed comparable blood circulation time, but $\sim 1.5$ times higher tumor targeting ability as compared to the PEGylated nanobody of comparable molecular weight. Our findings demonstrate that nanobody PASylation is a promising approach to produce long-circulating nanobody probes for imaging and therapeutic applications.

The aim of this study was to evaluate the role of low-density lipoproteins (LDLs) as a vehicle for aluminum sulfophthalocyanine (AlPcS) to target tumor cells for photodynamic therapy (PDT). LDLs are biological particles containing an apolipoprotein which recognizes with high affinity specific receptors on many cell types, including cancer cells. LDL was loaded with AlPcS in two different manners. In the first procedure, the tetrasulfonated AlPcS₄ was covalently bound to the protein part of the LDL via amide bonds to 6-carboxypentylaminosulfonyl spacer chains attached to two of the four sulfonate groups, i.e. AlPcS₄A₂. In the second procedure, the AlPcS₄ was substituted with a linear dodecylaminosulfonyl chain, i.e. AlPcS₄(C₁₂) and non-covalently inserted into the phospholipid monolayer of the LDL. Both preparations contained over 50 moles AlPcS/mole LDL. They were tested in vitro for their phototoxic properties against the EMT-6 mouse mammary tumor cell line and the A-549 human lung adenocarcinoma cell line. Cell survival was assessed using the MTT colorimetric assay. Association of the free AlPcS₄(C₁₂) with LDL increased the in vitro phototoxicity of the dye substantially against both cell lines while the covalently loaded AlPcS₄A₂-LDL preparation showed little cytotoxicity, even at a 10-fold-higher light or drug doses. It was postulated that the covalent labeling of the protein moiety with the Pc greatly reduced LDL receptor recognition, rendering this derivative photo-inactive. Photodynamic therapy of EMT-6 tumor-bearing mice showed that the free and LDL-associated AlPcS₄(C₁₂) exhibited similar activities, with 100% cure one week post-PDT at 0.2 μmol kg⁻¹. We conclude that the attached aliphatic chain of the AlPcS₄(C₁₂) greatly enhances the phototoxicity of the parent AlPcS₄ but that pre-association of the AlPcS₄(C₁₂) with LDL does not further augment its in vivo photodynamic efficacy.

Human gliomas are one of the most prevalent and challenging-to-treat adult brain tumors, and thus result in high morbidity and mortality rates worldwide. Current research and treatments of gliomas include surgery associated with conventional chemotherapy, use of biologicals, radiotherapy, and medical device applications. The selected treatment options are often guided by the category and aggressiveness of this deadly disease and the patient’s conditions. However, the effectiveness of these approaches is still limited due to poor drug efficacy (including delivery to desired sites), undesirable side effects, and high costs associated with therapies. In addition, the degree of leakiness of the blood–brain barrier (BBB) that regulates trafficking of molecules in and out of the brain also modulates accumulation of adequate drug levels to tumor sites. Active research is being pursued to overcome these limitations to obtain a superior therapeutic index and enhanced patient survival. One area of development in this direction focuses on the localized application of photodynamic therapy (PDT) drugs to cure brain cancers. PDT molecules potentially utilize multiple pathways based on their ability to generate reactive oxygen species (ROS) upon photoactivation by a suitable light source. In this communication, we have attempted to provide a brief overview of PDT and cancer, photoactivation pathways, mechanism of tumor destruction, effect of PDT on tumor cell viability, immune activation, various research attempted by applying PDT in combination with novel strategies to treat glioma, role of BBB and clinical status of PDT therapy for glioma treatment.

In the modern era, nanotechnology is one of the rapidly growing fields in many biomedical applications especially in delivering therapeutics for the curation of tumor cells. Cancer is a lethal disease that grows silently in the human body, caused by mutations in the genetic material of cells. The presence of a high number of physiologically active chemicals on the cancer cell surface does not particularly lead to tumor cell targeting. The lack of effective targeting of tumor cells by conventionally administered chemotherapeutic drugs demands the use of nanomedicine. Conventional medicines have immense cytotoxic effects, i.e., they do not kill tumor cells only but also destroy normal body cells. Nanoparticles (NPs) have an advantage over conventional therapeutic methods due to their small size, large surface area, and especially for targeting tumor cells without harming normal body cells. Based on durability and molecular weight, NPs are classified as organic and inorganic nanoparticles. Common organic and inorganic nanoparticles are highly effective against cancer curation and have high efficacy values along with their mechanism of action.

Our research has identified a couple of near-infrared (NIR) heptamethine indocyanine dyes exhibiting preferential tumor accumulation property for in vivo imaging. On the basis of our foregoing work, we describe here a preliminary structure–activity relationship (SAR) study of 11 related heptamethine indocyanine dyes and several essential requirements of these structures for in vivo tumor-targeted imaging.

Human gliomas are one of the most prevalent and challenging-to-treat adult brain tumors, and thus result in high morbidity and mortality rates worldwide. Current research and treatments of gliomas include surgery associated with conventional chemotherapy, use of biologicals, radiotherapy, and medical device applications. The selected treatment options are often guided by the category and aggressiveness of this deadly disease and the patient’s conditions. However, the effectiveness of these approaches is still limited due to poor drug efficacy (including delivery to desired sites), undesirable side effects, and high costs associated with therapies. In addition, the degree of leakiness of the blood–brain barrier (BBB) that regulates trafficking of molecules in and out of the brain also modulates accumulation of adequate drug levels to tumor sites. Active research is being pursued to overcome these limitations to obtain a superior therapeutic index and enhanced patient survival. One area of development in this direction focuses on the localized application of photodynamic therapy (PDT) drugs to cure brain cancers. PDT molecules potentially utilize multiple pathways based on their ability to generate reactive oxygen species (ROS) upon photoactivation by a suitable light source. In this communication, we have attempted to provide a brief overview of PDT and cancer, photoactivation pathways, mechanism of tumor destruction, effect of PDT on tumor cell viability, immune activation, various research attempted by applying PDT in combination with novel strategies to treat glioma, role of BBB and clinical status of PDT therapy for glioma treatment.