Cancer Theranostics Research Articles

Applications of nanomedicine-integrated phototherapeutic agents in cancer theranostics: A comprehensive review of the current state of research

Abstract Innovative approaches such as photodynamic therapy (PDT) and photothermal therapy (PTT) have made nanomedicines a promising frontier in cancer theranostics. The combination of nanocarriers with photothermal agents and photosensitizers (PSs) has shown excellent promise for the diagnosis and the treatment of cancer, primarily at the cellular, vascular, and tumor microenvironment level. Using nanocarriers in PDT has revolutionized precision and efficacy, allowing the drug to reach cancer cells faster and offering high enhancing PS accumulation. These agents are activated by light of specific wavelengths, leading to localized cytotoxicity, offering highly selective cancer therapy. Nanomaterials such as gold and silver nanoparticles have enabled remarkable progress in cancer hyperthermia using PTT. The unique optical properties of these nanoparticle-based nanomedicines make them ideal candidates for converting light energy into heat, selectively ablating the cancer cells. In this review, nanomedicine-integrated phototherapeutic agents are discussed and the most important recent developments in PDT and PTT are examined, as well as how nanoparticle-based formulations improve diagnosis and treatment. In addition, nanocarriers used in cancer phototherapy and their mode of action are discussed. Nanocarriers are useful for drug delivery as well as for imaging and diagnostic purposes during cancer treatment. In this review, we explore the role of nanoparticles in improving phototherapy precision and selectivity while minimizing collateral tissue damage. It specifies a comprehensive impression of the current research on cancer therapy, underscoring its potential to revolutionize the treatment paradigm by highlighting the current state of research.

Tumor versus Tumor Cell Targeting in Metal-Based Nanoparticles for Cancer Theranostics.

The application of metal-based nanoparticles (mNPs) in cancer therapy and diagnostics (theranostics) has been a hot research topic since the early days of nanotechnology, becoming even more relevant in recent years. However, the clinical translation of this technology has been notably poor, with one of the main reasons being a lack of understanding of the disease and conceptual errors in the design of mNPs. Strikingly, throughout the reported studies to date on in vivo experiments, the concepts of "tumor targeting" and "tumor cell targeting" are often intertwined, particularly in the context of active targeting. These misconceptions may lead to design flaws, resulting in failed theranostic strategies. In the context of mNPs, tumor targeting can be described as the process by which mNPs reach the tumor mass (as a tissue), while tumor cell targeting refers to the specific interaction of mNPs with tumor cells once they have reached the tumor tissue. In this review, we conduct a critical analysis of key challenges that must be addressed for the successful targeting of either tumor tissue or cancer cells within the tumor tissue. Additionally, we explore essential features necessary for the smart design of theranostic mNPs, where 'smart design' refers to the process involving advanced consideration of the physicochemical features of the mNPs, targeting motifs, and physiological barriers that must be overcome for successful tumor targeting and/or tumor cell targeting.

Smart Multifunctional Nanoparticles in Cancer Theranostics: Progress and Prospect.

Worldwide, cancer is the second most common cause of death. Chemotherapy and other traditional cancer treatments have toxicities that affect normal cells in addition to their intended targets, necessitating the development of novel approaches to enhance cell-specific targeting. The present work summarizes the scientific information on nanoparticles in cancer theranostics to provide a comprehensive insight into the preventive and therapeutic potential of nanoparticles in cancer. Scopus, PubMed, Science Direct, and Google Scholar databases are searched to collect all the recent (2015-2023) scientific information on smart multifunctional nanoparticles using the terms nanotechnology, cancer theranostics, and polymer. The use of nanomaterials as chemical biology tools in cancer theranostics has been thoroughly investigated. They demonstrate expanded uses in terms of stability, biocompatibility, and enhanced cell permeability, enabling precision targeting and ameliorating the drawbacks of conventional cancer treatments. The nano platform presents a fascinating chance to acquire multifunctionality and targeting techniques. The production of smart nanomaterials, specifically with regard to the advent of nanotechnology, has revolutionized the diagnosis and treatment of cancer. The capability of nanoparticles to functionalize with a variety of biosubstrates, including aptamers, antibodies, DNA, and RNA, and their broad surface area allow them to encapsulate a huge number of molecules, contributing to their theranostic effect. Comparatively speaking, economical, easily produced, and less toxic nanomaterials formed from biological sources are thought to have benefits over those made using conventional processes. The present study highlights the uses of several nanoparticles (NPs), and describes numerous cancer theranostics methodologies. The benefits and difficulties preventing their adoption in cancer treatment and diagnostic applications are also critically reviewed. The use of smart nanomaterials, according to this review's findings, can considerably advance cancer theranostics and open up new avenues for tumor detection and treatment.

Current Expansion of Silver and Gold Nanomaterials towards Cancer Theranostics: Development of Therapeutics

Abstract: Nanomaterial-based therapeutics is an emerging tool for the treatment of numerous types of cancer. Various types of polymeric, lipid and inorganic nanoparticles (NPs) result in a wider series of applications in cancer diagnosis and therapeutics. The NPs properties are due to high surface area to volume ratio, surface plasmon resonance, absorption in the visible spectrum and light scattering. These unique characteristics of NPs arise due to their optical surface properties for conjugation/surface modification and smaller size. In cancer therapeutics, NPs based products are used as a biomarker for early detection/diagnosis of tumours, drug nano-conjugates for the delivery of chemotherapeutic drugs to the tumour-specific site, chemo-protective agents, etc. : Furthermore, other advantages of NPs are biocompatibility, lesser toxicity, enhanced permeability and retention effect, higher stability, and specific targeting with a selective accumulation of nano drugs in the tissue of the tumour. The selective targeting of NPs to tumour tissue is possible by adding surface-active targeting agents i.e., antibodies. The selective transport of drug NPs conjugates to the cancer cells is increased and extravagated due to permeable vasculature from endothelial cells gap while failing the transport of drug NPs conjugates in normal cells. This review emphasizes metallic NPs, including silver NPs (AgNPs) and gold NPs (AuNPs), which are extensively reconnoitered in various applications in cellular targeting, imaging, drug delivery, DNA-NPs conjugates for biosensor/point of care devices development, photothermal/photodynamic therapy, protein-protein interaction, etc. In addition, this review discussed different synthetic methods of AgNPs and AuNPs and characterization methods. Furthermore, it highlighted the different properties and applications of AgNPs and AuNPs in cancer theranostics.

Nuclear Medicine Cancer Care-Current Status and Future Directions for Radiopharmaceutical Diagnostics and Theranostics for Cancer.

Nuclear Medicine Cancer Care-Current Status and Future Directions for Radiopharmaceutical Diagnostics and Theranostics for Cancer.

Fibroblast Activation Protein Inhibitor Tracers and Their Preclinical, Translational, and Clinical Status in China.

Quinoline-based fibroblast activation protein (FAP) inhibitors (FAPIs) have recently emerged as a focal point in global nuclear medicine, underscored by their promising applications in cancer theranostics and the diagnosis of various nononcological conditions. This review offers an in-depth summary of the existing literature on the evolution and use of FAPI tracers in China, tracing their journey from preclinical to clinical research. Moreover, this review also assesses the diagnostic accuracy of FAPI PET for the most common cancers in China, analyzes its impact on oncologic management paradigms, and investigates the potential of FAP-targeted radionuclide therapy in patients with advanced or metastatic cancer. This review also summarizes studies using FAPI PET for nononcologic disorders in China. Thus, this qualitative overview presents a snapshot of China's engagement with FAPI tracers, aiming to guide future research endeavors.

Combing NIR-II molecular dye with magnetic nanoparticles for enhanced photothermal theranostics with a 95.6% photothermal conversion efficiency

Photoheranostics have emerged as a promising tool for cancer theranostics owing to their real-time feedback on treatment and their precise diagnosis. Among them, how to improve the photothermal conversion efficiency (PCE) of phototheranostic agents (PTAs) is the key factor for phototheranostic systems. Herein, we provided an efficient method to improve PCE and constructed a biocompatible nano-material ICR-Qu@NH2-Fe3O4@PEG (QNFP) by combing near-infrared second region (NIR-II) molecular dye ICR-Qu and amino-modified magnetic nanoparticles and then encapsulated by DSPE-mPEG2000. QNFP exhibited excellent performance for photothermal therapy with a high PCE of 95.6%. Both in vitro and in vivo experiments indicated that QNFP could inhibit the growth of tumors under laser irradiation with low toxicity and realized real-time NIR-II fluorescent imaging of tumors. In general, we realized a simple but efficient method to improve the PCE of NIR-II molecular dye without reduce its quantum yield, which is an ideal choice for cancer diagnosis and treatment.

Drug-loaded polymer-coated silver nanoparticles for lung cancer theranostics.

Lung cancer is the leading cause of death in cancer across the globe. To minimize these deaths, the replacement of traditional chemotherapy with novel strategies is significant. We have developed a nanotheranostic approach using silver nanoparticles for imaging and treatment. Silver nanoparticles (AgNPs) are fabricated by chemical reduction method. The formulation of AgNPs was confirmed by different characterization techniques like stability test, UV-Visible spectroscopy, Confocal Raman Spectroscopy, and Energy-Dispersive X-ray analysis. Further, AgNPs are coated with poly lactic-co-glycolic acid (PLGA) and then loaded with paclitaxel(Pac). Then the drug-loaded PLGA-coated AgNPs were characterized for size and zeta potential measurement by zetasizer, surface morphology study by atomic force microscopy, Fourier transform infrared spectroscopy, and release kinetics study. The imaging and anticancer properties of these nanoformulations are investigated using lung cancer cell lines. The results proved that the particles are in the nanometer range with smooth surface morphology. Moreover, the drug-loaded NPs showed a sustained release of the drug for a longer period of time. Further the formulations showed imaging property with greater anticancer efficacy. Thus, the results suggest the effective use of these nanoformulation in both lung cancer imaging and treatment using a simple and efficient approach.

Recent Progress on Second Near-Infrared Emitting Carbon Dots in Biomedicine.

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.

Polymersomes: A Novel Approach for Cancer Theranostics

Background: In the recent epochs of advancement in the field of oncology, polymersomes- based drug delivery systems have witnessed a significant breakthrough. Nano-sized carriers formed from amphiphilic block-copolymers, have distinctive compositions and structures, enabling them to encapsulate a diverse range of compounds. Objective: This comprehensive review aims to highlight the significant advancements reflecting progress made in the past few decades and their potential in cancer treatments, offering a promising future for improved patient outcomes and as a tool for theranostics. Method: Different approaches for synthesizing nanocarriers with distinct responsive characteristics have been mentioned. Redox-responsive polymersomes are designed, and their self-assembly behavior is studied. pH-responsive are created using specific copolymers, while enzyme-responsive ones are engineered to degrade in the presence of lysosomal enzymes using various approaches like thin-film hydration, nanoprecipitation, etc. Result: Polymersomes have exhibited remarkable breakthroughs in cancer theranostics and addressed various challenges associated with drug targeting, diminishing the toxicity, and related issues, exhibiting advantages such as enhanced stability, prolonged circulation time, and the ability to encapsulate both hydrophilic and hydrophobic substances. Over the past few decades, they have been proven as a breakthrough approach for cancer therapy. Conclusion: Polymersomes present a promising platform for advancing cancer therapeutics and diagnostics, offering a multifunctional approach that combines targeted drug delivery with imaging capabilities. Their versatility makes them valuable tools for researchers and practitioners in the field of medicine.

PSMA-reactive NB7 single domain antibody fragment: A potential scaffold for developing prostate cancer theranostics

IntroductionSingle domain antibody fragments (sdAbs) are an appealing scaffold for radiopharmaceutical development due to their small size (~15 kDa), high solubility, high stability, and excellent tumor penetration. Previously, we developed NB7 sdAb, which has very high affinity for an epitope on PSMA that is different from those targeted by small molecule PSMA inhibitors. Herein, we evaluated NB7 after radioiodination using [*I]SGMIB (1,3,4-isomer) and iso-[*I]SGMIB (1,3,5-isomer), as well as their 211At-labeled analogues. Methods[*I]SGMIB, iso-[*I]SGMIB, [211At]SAGMB, and iso-[211At]SAGMB conjugates of NB7 sdAb were synthesized and their binding affinity, cell uptake and internalization were assessed in PSMA+ PC3 PIP and PSMA− PC3 flu cells. Biodistribution studies were performed in mice bearing PSMA+ PC3 PIP xenografts. First, a single-label experiment evaluated the tissue distribution of a NB7 bearing a His6-tag (NB7H6) and labeled with iso-[125I]SGMIB. Three paired-label experiments then were performed to compare: a) NB7 labeled using [*I]SGMIB and iso-[*I]SGMIB, b) 131I- vs 211At-labeled NB7 conjugates and c) [125I]SGMIB-NB7H6 to the small molecule PSMA inhibitor [131I]YF2. ResultsAll NB7 radioconjugates bound specifically to PSMA with dissociation constants, Kd, in the low nM range (1.4–6.4 nM). An initial biodistribution study demonstrated good tumor uptake for iso-[125I]SGMIB-NB7H6 (7.2 ± 1.5 % ID/g at 1 h) and no deleterious effect of the His6-tag on renal activity levels, which declined to 3.1 ± 1.1 % ID/g by 4 h. Paired-label biodistribution found no distinction between the two SGMIB isomer NB7 conjugates with the [131I]SGMIB-NB7-to-iso-[125I]SGMIB-NB7 tumor uptake ratios not significantly different from unity: 1.06 ± 0.08 at 1 h, 1.04 ± 0.12 at 4 h, and 1.07 ± 0.09 at 24 h. Both isomer conjugates cleared rapidly from normal tissues and exhibited very low uptake in thyroid, lacrimal and salivary glands. Paired-label biodistribution of [131I]SGMIB-NB7H6 and [211At]SAGMB-NB7H6 demonstrated similar tumor uptake and kidney clearance for the two radioconjugates. However, levels of 211At in thyroid, stomach, salivary and lacrimal glands were significantly higher (P < 0.05) that those for 131I suggesting greater dehalogenation for [211At]SAGMB-NB7H6. Finally, co-administration of [125I]SGMIB-NB7H6 and [131I]YF2 demonstrated good tumor uptake for both with considerably more rapid renal clearance for the NB7 radioconjugate. ConclusionNB7 radioconjugates exhibited good accumulation in PSMA-positive xenografts with rapid clearance from kidney and other normal tissues. We conclude that NB7 is a potentially useful scaffold for developing PSMA-targeted theranostics with different characteristics than current small molecule and antibody-based approaches.

A mesoporous superparamagnetic iron oxide nanoparticle as a generic drug delivery system for tumor ferroptosis therapy

As a famous drug delivery system (DDS), mesoporous organosilica nanoparticles (MON) are degraded slowly in vivo and the degraded components are not useful for cell nutrition or cancer theranostics, and superparamagnetic iron oxide nanoparticles (SPION) are not mesoporous with low drug loading content (DLC). To overcome the problems of MON and SPION, we developed mesoporous SPIONs (MSPIONs) with an average diameter of 70 nm and pore size of 3.9 nm. Sorafenib (SFN) and/or brequinar (BQR) were loaded into the mesopores of MSPION, generating SFN@MSPION, BQR@MSPION and SFN/BQR@MSPION with high DLC of 11.5% (SFN), 10.1% (BQR) and 10.0% (SNF + BQR), demonstrating that our MSPION is a generic DDS. SFN/BQR@MSPION can be used for high performance ferroptosis therapy of tumors because: (1) the released Fe2+/3+ in tumor microenvironment (TME) can produce •OH via Fenton reaction; (2) the released SFN in TME can inhibit the cystine/glutamate reverse transporter, decrease the intracellular glutathione (GSH) and GSH peroxidase 4 levels, and thus enhance reactive oxygen species and lipid peroxide levels; (3) the released BQR in TME can further enhance the intracellular oxidative stress via dihydroorotate dehydrogenase inhibition. The ferroptosis therapeutic mechanism, efficacy and biosafety of MSPION-based DDS were verified on tumor cells and tumor-bearing mice.

Navigating through the coordination preferences of heavy alkaline earth metals: Laying the foundations for 223Ra- and 131/135mBa-based targeted alpha therapy and theranostics of cancer

The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted.This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV–Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.

Methotrexate-loaded manganese nitrogen dual-doped carbon quantum dots as targeted nano drug-delivery system for potential use in cancer theranostics

The present work highlights manganese nitrogen dual-doped carbon quantum dots as a novel pH-sensitive drug delivery system, for the delivery of methotrexate, targeted to cancer cells, along with the simultaneous real-time monitoring of cellular uptake and drug delivery using fluorescence imaging. Briefly, methotrexate was conjugated with the as-prepared quantum dots to form a nano drug-delivery system through non-covalent interactions. The developed material demonstrated drug loading efficiency of ∼91 % and a very efficient (∼80 %) pH-responsive drug release at pH 5.5. The cytotoxic properties of the developed nano-platform viz. manganese, nitrogen dual-doped carbon quantum dots, and methotrexate conjugated manganese nitrogen dual-doped carbon quantum dot complex were evaluated in cancer cells (HeLa) and healthy human cells (L929). The conjugated complex demonstrated excellent biocompatibility, high cellular uptake, and a substantial drug release. Healthy human cells were largely unaffected when incubated with both the MTX-conjugated Mn-, N-CQD and the free drug. Additionally, in vitro, the fluorescence bio-imaging potential of the developed nano-platform was also assessed, where the unconjugated (free) quantum dots exhibited better blue fluorescence imaging potential compared to that of the conjugated complex, which can be attributed to fluorescence quenching due to the presence of methotrexate. This study highlights the manganese nitrogen dual-doped carbon quantum dots capable of pH-responsive methotrexate drug delivery selective to cancer cells. The combination of drug delivery and fluorescence imaging creates an efficient platform for targeted therapy, allowing very precise drug release while accessing non-invasive monitoring of therapeutic response. This method holds a great promise for advancing cancer treatment strategies, with the potential for increased efficacy and decreased side effects.

Quantum Dots in Cancer Theranostics: A Thorough Review of Recent Advancements in Bioimaging, Tracking, and Therapy across Various Cancer Types.

Quantum dots (QDs) have attracted considerable interest due to their potential applications and economic viability in various industrial sectors, such as communications, displays, and solar cells. This fascination originates from the quantum size effect-induced remarkable optical properties exhibited by QDs. In recent years, significant progress has been made in producing QDs devoid of cadmium, known to be toxic to cells and living organisms. These QDs have generated considerable interest in bioimaging due to their potential for targeting molecules and cells. There is a developing need for diagnostics and therapy at the individual molecule and single-cell level in the medical field. As a result, the application of QDs in the medical industry is gaining momentum. This study provides an overview of the most recent developments in applying QDs for diagnostic and therapeutic purposes, also known as theranostics. It emphasizes specifically the use of QDs in cancer therapy.

Current state of theranostics in metastatic castrate-resistant prostate cancer.

Prostate cancer remains one of the leading causes of cancer-related death in the world. There have been significant advances in chemotherapy, hormonal therapy and targeted therapy options for patients with castrate-resistant disease. However, these systemic treatments are often associated with unwanted toxicities. Targeted therapy with radiopharmaceuticals has become of key interest to limit systemic toxicity and provides a more precision oncology approach to treatment. Strontium-89, Samarium-153 EDTMP and Radium-223 have been trialled with mixed results. Strontium-89 and Samarium-153 EDTMP have shown benefits in palliating metastatic bone pain but with no impact on survival outcomes. Early therapeutic radiopharmaceuticals targeting PSMA that were developed were beta-emitting agents, but recently alpha-emitting agents are being investigated as potentially superior options. Radium-223 is the first alpha-particle emitter therapeutic agent approved by the FDA, with phase III trial evidence showing benefits in overall survival and delay in symptomatic skeletal events for patients. Recently, 177-Lutetium-PSMA-617 has demonstrated significant survival advantages in pre-treated metastatic castrate-resistant cancer patients in a number of phase II and III studies. Furthermore, 225-Actinium-PSMA-617 also showed promise even in patients pre-treated with 177-Lutetium-PSMA-617. Hence, there has been an explosion of radiopharmaceutical treatment options for patients with prostate cancer. This review explores past and current theranostic capacities in the radiopharmaceutical treatment of metastatic castrate-resistant prostate cancer.

Synthesis and characterization of a bifunctional platform based on magnetite-gold nanoparticles for theranostics of cancer

Synthesis and characterization of a bifunctional platform based on magnetite-gold nanoparticles for theranostics of cancer

Recent Insights into Glucose-Responsive Concanavalin A-Based Smart Hydrogels for Controlled Insulin Delivery.

Many efforts are continuously undertaken to develop glucose-sensitive biomaterials able of controlling glucose levels in the body and self-regulating insulin delivery. Hydrogels that swell or shrink as a function of the environmental free glucose content are suitable systems for monitoring blood glucose, delivering insulin doses adapted to the glucose concentration. In this context, the development of sensors based on reversible binding to glucose molecules represents a continuous challenge. Concanavalin A (Con A) is a bioactive protein isolated from sword bean plants (Canavalia ensiformis) and contains four sugar-binding sites. The high affinity for reversibly and specifically binding glucose and mannose makes Con A as a suitable natural receptor for the development of smart glucose-responsive materials. During the last few years, Con A was used to develop smart materials, such as hydrogels, microgels, nanoparticles and films, for producing glucose biosensors or drug delivery devices. This review is focused on Con A-based materials suitable in the diagnosis and therapeutics of diabetes. A brief outlook on glucose-derived theranostics of cancer is also presented.

GRPR-Antagonists Carrying DOTAGA-Chelator via Positively Charged Linkers: Perspectives for Prostate Cancer Theranostics.

Gastrin-releasing peptide receptor (GRPR)-antagonists have served as motifs in the development of theranostic radioligands for prostate cancer. Our efforts have been focused on the development of radiolabeled RM26 (H-DPhe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) analogs, such as [111In]In-DOTAGA-PEG2-RM26. We recently showed that its Gly11/Sar11-substituted version, [111In]In-AU-RM26-M1, resisted degradation by neprilysin (NEP) while in circulation and achieved higher tumor uptake in mice. We herein introduce the following three new AU-RM26-M1 mimics labeled with In-111, with basic residues in the linker: (i) AU-RM26-M2 (PEG2-Pip), (ii) AU-RM26-M3 (PEG2-Arg), and (iii) AU-RM26-M4 (Arg-Arg-Pip). These analogs were compared in PC-3 cells and animal models vs. AU-RM26-M1 (reference). The new analogs showed high affinity and specificity for the GRPR, exhibiting an uptake and distribution pattern in PC-3 cells typical for a radiolabeled GRPR-antagonist. They showed high stability in peripheral mice blood, except for [111In]In-AU-RM26-M3. AU-RM26-M4 achieved the highest tumor uptake and promising background clearance, followed by [111In]In-RM26-M2, showing lower background levels. These findings were confirmed for [111In]In-AU-RM26-M2 and [111In]In-AU-RM26-M4 by micro-SPECT/CT at 4 and 24 h post-injection. Hence, the type of positively charged residues in the linker of AU-RM26-M1 mimics strongly influenced biological behavior. The analogs with Pip next to DPhe6 demonstrated the best overall characteristics and warrant further investigation.

О возможности использования иттербиевого комплекса 2,4-ди (α-метоксиэтил)дейтеропорфирина IX для тераностики новообразований поверхностной локализации

The dynamics of the photosensitized singlet oxygen formation for the ytterbium 2,4-di(α-methoxyethyl)deuteroporphyrin IX complex (Yb-DMDP IX) and for its metal-free form under laser excitation on a highly sensitive laser fluorimeter was studied. It has been shown that the quantum yield of singlet oxygen generation for Yb-DMDP IX (11%) is significantly lower than in the case of DMDP IX itself (40%), which experimentally confirms the low phototoxicity of the Yb complex. However, the established 11% quantum yield of 1O2 indicates the possible presence of DMDP IX in the main substance of Yb-DMDP IX, leading to residual phototoxicity. Using high-performance liquid chromatography, the quantitative ratios of the Yb-complex and its metal-free form (10%) were established. Thus, the presented Yb-complex can also be used for cancer theranostics, since after carrying out IR luminescence diagnostics (in the 900–1100 nm spectral range), it is also possible to subsequently carry out the PDT procedure in the absorption band of the porphyrin complex metal-free form at the 630 nm wavelength. The Yb-DMDP IX effectiveness for the PDT procedure can be significantly increased by treating this compound with ascorbic acid after the IR luminescence diagnostics procedure.