9 research outputs found
Fungal Enzyme l-Lysine Ξ±-Oxidase Affects the Amino Acid Metabolism in the Brain and Decreases the Polyamine Level
The fungal glycoprotein l-lysine Ξ±-oxidase (LO) catalyzes the oxidative deamination of l-lysine (l-lys). LO may be internalized in the intestine and shows antitumor, antibacterial, and antiviral effects in vivo. The main mechanisms of its effects have been shown to be depletion of the essential amino acid l-lys and action of reactive oxidative species produced by the reaction. Here, we report that LO penetrates into the brain and is retained there for up to 48 h after intravenous injection, which might be explained by specific pharmacokinetics. LO actively intervenes in amino acid metabolism in the brain. The most significant impact of LO was towards amino acids, which are directly exposed to its action (l-lys, l-orn, l-arg). In addition, the enzyme significantly affected the redistribution of amino acids directly associated with the tricarboxylic acid (TCA) cycle (l-asp and l-glu). We discovered that the depletion of l-orn, the precursor of polyamines (PA), led to a significant and long-term decrease in the concentration of polyamines, which are responsible for regulation of many processes including cell proliferation. Thus, LO may be used to reduce levels of l-lys and PA in the brain
ΠΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π²ΠΎΠ΄ΠΎΡΠ°ΡΡΠ²ΠΎΡΠΈΠΌΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΡ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΎΠ² Π² ΡΠΎΠ½ΠΊΠΎΠΉ ΠΊΠΈΡΠΊΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡ-ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ex vivo Ρ ΠΏΠΎΠΌΠΎΡΡΡ Ρ Π΅ΠΌΠΈΠ»ΡΠΌΠΈΠ½Π΅ΡΡΠ΅Π½ΡΠΈΠΈ
Introduction. The ability of the small intestine (internalization) to absorb water-soluble anticancer cytostatics determines the possibility of their oral administration. The ex-vivo express method that simulates the internalization of substances using a modified technique of an isolated Β«invertedΒ» segment of the rat small intestine with flash chemiluminescence is adequate to solve the problem. Objectives: to evaluate the absorption of the new water-soluble anticancer cytostatics with different properties from the rat small intestine for preclinical study by oral administration. Material and Methods. Conjugated with acridinium (Acridinium NHS Ester, Toronto Research Chemicals, Canada) cytostatics were studied: low molecular weight (1) Anthrafuran-Acridinium (MW 0.8 kDa) and high molecular weight (2) Aimpila-Acridinium (MW 105 kDa) and (3) L-lysine-a-oxidase (LO-Acridinium, MW 122 kDa). Absorption was determined in a modified model of an isolated Β«invertedΒ» segment of the rat small intestine using flash-chemiluminescence with the calculation of the relative light units (RLU). Results. It was shown that the absorption level of acridinium-conjugated cytostatics depending on molar concentration ranged from 55 % (1) to 1.7-11 % (2, 3) and 2500 (1) to 9.2-188 nmol/l (2, 3), respectively. The level of internalized Anthrafuran-Acridinium (55 %) was consistent with the known value of the effective non-conjugated cytostatic oral dose, which was two times higher than equitherapeutical parenteral dose: 100 mg/kg vs 50 mg/kg. Conclusion. The data obtained allow us to consider ex vivo express method for preclinical study of the various water-soluble anticancer cytostatics for screening and identification of an opportunity for oral administration and estimation of starting dose. The method has a good correlation with in vivo tests and economically favorable due to a quick response and small number of the tested agent.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π‘ΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊ Π²ΡΠ°ΡΡΠ²Π°Π½ΠΈΡ Π² ΡΠΎΠ½ΠΊΠΎΠΉ ΠΊΠΈΡΠΊΠ΅ (ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ) Π²ΠΎΠ΄ΠΎΡΠ°ΡΡΠ²ΠΎΡΠΈΠΌΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΎΠ² ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΈΡ
ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ. ΠΠΊΡΠΏΡΠ΅ΡΡ-ΠΌΠ΅ΡΠΎΠ΄ ex vivo, ΠΌΠΎΠ΄Π΅Π»ΠΈΡΡΡΡΠΈΠΉ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ Π²Π΅ΡΠ΅ΡΡΠ² Π² ΡΠ°ΠΌΠΊΠ°Ρ
ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΌΠ΅ΡΠΎΠ΄ΠΈΠΊΠΈ ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Β«Π²ΡΠ²Π΅ΡΠ½ΡΡΠΎΠ³ΠΎΒ» ΠΎΡΡΠ΅Π·ΠΊΠ° ΡΠΎΠ½ΠΊΠΎΠΉ ΠΊΠΈΡΠΊΠΈ ΠΊΡΡΡΡ Ρ ΠΈΠΌΠΏΡΠ»ΡΡΠ½ΠΎΠΉ Ρ
Π΅ΠΌΠΈΠ»ΡΠΌΠΈΠ½Π΅ΡΡΠ΅Π½ΡΠΈΠ΅ΠΉ, Π°Π΄Π΅ΠΊΠ²Π°ΡΠ΅Π½ Π΄Π»Ρ ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΏΠΎΡΡΠ°Π²Π»Π΅Π½Π½ΠΎΠΉ Π·Π°Π΄Π°ΡΠΈ. Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ - ΠΎΡΠ΅Π½ΠΊΠ° Π²ΡΠ°ΡΡΠ²Π°Π½ΠΈΡ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌ ΠΈΠ· ΡΠΎΠ½ΠΊΠΎΠΉ ΠΊΠΈΡΠΊΠΈ Π½ΠΎΠ²ΡΡ
Π²ΠΎΠ΄ΠΎΡΠ°ΡΡΠ²ΠΎΡΠΈΠΌΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΎΠ² Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ Π΄Π»Ρ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΠΏΡΠΈ ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΠΊΠ»ΡΡΠ΅Π½Ρ ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ Ρ ΠΠΊΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ (Acridinium NHS Ester, Toronto Research Chemicals, Canada) ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΈ: Π½ΠΈΠ·ΠΊΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΉ (1) ΠΠ½ΡΡΠ°ΡΡΡΠ°Π½-ΠΠΊΡΠΈΠ΄ΠΈΠ½ (MW 0,8 ΠΊΠΠ°) ΠΈ Π²ΡΡΠΎΠΊΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠ΅ (2) ΠΠΈΠΌΠΏΠΈΠ»Π°-ΠΠΊΡΠΈΠ΄ΠΈΠ½ (MW 105 ΠΊΠΠ°) ΠΈ (3) L-Π»ΠΈΠ·ΠΈΠ½-Π°-ΠΎΠΊΡΠΈΠ΄Π°Π·Π° (ΠΠ-ΠΠΊΡΠΈΠ΄ΠΈΠ½, MW 122 ΠΊΠΠ°). ΠΡΠ°ΡΡΠ²Π°Π½ΠΈΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΎ Π² ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΈΠ·ΠΎΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Β«Π²ΡΠ²Π΅ΡΠ½ΡΡΠΎΠ³ΠΎΒ» ΠΎΡΡΠ΅Π·ΠΊΠ° ΡΠΎΠ½ΠΊΠΎΠΉ ΠΊΠΈΡΠΊΠΈ ΠΊΡΡΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΠΌΠΏΡΠ»ΡΡΠ½ΠΎΠΉ ΡΠ»ΡΡ-Ρ
Π΅ΠΌΠΈΠ»ΡΠΌΠΈΠ½Π΅ΡΡΠ΅Π½ΡΠΈΠΈ ΠΈ ΠΏΠ΅ΡΠ΅ΡΡΠΈΡΠ°Π½ΠΎ Π² ΠΏΡΠΎΡΠ΅Π½ΡΠ°Ρ
. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΠΌΠΎΠ»ΡΡΠ½ΠΎΠΉ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈΠΈ ΠΎΡ 2500 (1) Π΄ΠΎ 9,2-188 Π½ΠΌΠΎΠ»Ρ/Π» (2, 3) ΡΡΠΎΠ²Π΅Π½Ρ Π²ΡΠ°ΡΡΠ²Π°Π½ΠΈΡ ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½-Π½ΡΡ
Ρ ΠΠΊΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΎΠ² Π½Π°Ρ
ΠΎΠ΄ΠΈΡΡΡ Π² Π΄ΠΈΠ°ΠΏΠ°Π·ΠΎΠ½Π΅ ΠΎΡ 55 % (1) Π΄ΠΎ 1,7-11 % (2, 3) ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. Π£ΡΠΎΠ²Π΅Π½Ρ Π²ΡΠ°ΡΡΠ²Π°Π½ΠΈΡ ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΠ½ΡΡΠ°ΡΡΡΠ°Π½Π° (55 %) ΡΠΎΠ³Π»Π°ΡΡΠ΅ΡΡΡ Ρ Π²Π΅Π»ΠΈΡΠΈΠ½ΠΎΠΉ ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΎΠ·Ρ Π½Π΅ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠ°, ΠΊΠΎΡΠΎΡΠ°Ρ Π±ΡΠ»Π° Π² Π΄Π²Π° ΡΠ°Π·Π° Π±ΠΎΠ»ΡΡΠ΅, ΡΠ΅ΠΌ ΡΠΊΠ²ΠΈΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΏΠ°ΡΠ΅Π½ΡΠ΅ΡΠ°Π»ΡΠ½Π°Ρ Π΄ΠΎΠ·Π°: 100 ΠΌΠ³/ΠΊΠ³ ΠΏΡΠΎΡΠΈΠ² 50 ΠΌΠ³/ΠΊΠ³. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡ-ΠΌΠ΅ΡΠΎΠ΄ ex vivo Π΄Π»Ρ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ Π΄ΠΎΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ
Π²ΠΎΠ΄ΠΎΡΠ°ΡΡΠ²ΠΎΡΠΈΠΌΡΡ
ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΡ
ΡΠΈΡΠΎΡΡΠ°ΡΠΈΠΊΠΎΠ² ΠΏΡΠΈ ΠΏΠ΅ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΡΠ°ΡΡΠΎΠ²ΠΎΠΉ Π΄ΠΎΠ·Ρ. ΠΠ΅ΡΠΎΠ΄ Π°Π΄Π΅ΠΊΠ²Π°ΡΠ΅Π½ ΡΠ΅ΡΡΠ°ΠΌ in vivo ΠΈ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠΈ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π΅Π½ Π² ΡΠΈΠ»Ρ Π±ΡΡΡΡΠΎΠ³ΠΎ ΠΎΡΠ²Π΅ΡΠ° ΠΈ ΠΌΠ°Π»ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΡΠ΅ΡΡΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ Π°Π³Π΅Π½ΡΠ°
Photoluminescent Scaffolds Based on Natural and Synthetic Biodegradable Polymers for Bioimaging and Tissue Engineering
Non-invasive visualization and monitoring of tissue-engineered structures in a living organism is a challenge. One possible solution to this problem is to use upconversion nanoparticles (UCNPs) as photoluminescent nanomarkers in scaffolds. We synthesized and studied scaffolds based on natural (collagenβCOL and hyaluronic acidβHA) and synthetic (polylactic-co-glycolic acidsβPLGA) polymers loaded with Ξ²-NaYF4:Yb3+, Er3+ nanocrystals (21 Β± 6 nm). Histomorphological analysis of tissue response to subcutaneous implantation of the polymer scaffolds in BALB/c mice was performed. The inflammatory response of the surrounding tissues was found to be weak for scaffolds based on HA and PLGA and moderate for COL scaffolds. An epi-luminescent imaging system with 975 nm laser excitation was used for in vivo visualization and photoluminescent analysis of implanted scaffolds. We demonstrated that the UCNPsβ photoluminescent signal monotonously decreased in all the examined scaffolds, indicating their gradual biodegradation followed by the release of photoluminescent nanoparticles into the surrounding tissues. In general, the data obtained from the photoluminescent analysis correlated satisfactorily with the histomorphological analysis
Photoluminescent Scaffolds Based on Natural and Synthetic Biodegradable Polymers for Bioimaging and Tissue Engineering
Non-invasive visualization and monitoring of tissue-engineered structures in a living organism is a challenge. One possible solution to this problem is to use upconversion nanoparticles (UCNPs) as photoluminescent nanomarkers in scaffolds. We synthesized and studied scaffolds based on natural (collagenβCOL and hyaluronic acidβHA) and synthetic (polylactic-co-glycolic acidsβPLGA) polymers loaded with Ξ²-NaYF4:Yb3+, Er3+ nanocrystals (21 Β± 6 nm). Histomorphological analysis of tissue response to subcutaneous implantation of the polymer scaffolds in BALB/c mice was performed. The inflammatory response of the surrounding tissues was found to be weak for scaffolds based on HA and PLGA and moderate for COL scaffolds. An epi-luminescent imaging system with 975 nm laser excitation was used for in vivo visualization and photoluminescent analysis of implanted scaffolds. We demonstrated that the UCNPsβ photoluminescent signal monotonously decreased in all the examined scaffolds, indicating their gradual biodegradation followed by the release of photoluminescent nanoparticles into the surrounding tissues. In general, the data obtained from the photoluminescent analysis correlated satisfactorily with the histomorphological analysis
Antitumor Effect of Bleomycin Nanoaerosol in Murine Carcinoma Model
Bleomycin, which is widely used as an antitumor agent, possesses serious adverse effects such as pulmonary toxicity. Local nanoaerosol deposition for lung cancer treatment is a promising alternative to drug delivery to lung lesions. The aim of this work is to test the hypothesis that bleomycin nanoaerosol can be effectively used to treat multiple lung metastases. To obtain bleomycin nanoaerosol, an aerosol generator based on electrospray of a solution of a nonvolatile substance with gas-phase neutralization of charged aerosol particles was used. Lung metastases in murine Lewis lung carcinoma and B16 melanoma animal models were counted. The effect of inhaled bleomycin nanoparticles on the number and volume of metastases, as well as pulmonary side effects, was investigated. Using a mouse exposure chamber, the dose-dependent effect of inhaled bleomycin on tumor volume was evaluated in comparison with intraperitoneal administration. Bleomycin nanoaerosol reduced the volume of metastases and produced a higher antitumor effect at much lower doses. It has been established that long-term exposure to nanoaerosol with a low dose of bleomycin is capable of suppressing cancer cell growth. The treatment was well tolerated. In the lungs, minor changes were found in the form of focal-diffuse infiltration of the lung parenchyma
Bioactivity Features of a Zn-1%Mg-0.1%Dy Alloy Strengthened by Equal-Channel Angular Pressing
The structure, phase composition, corrosion and mechanical properties, as well as aspects of biocompatibility in vitro and in vivo, of a Zn-1%Mg-0.1%Dy alloy after equal-channel angular pressing (ECAP) were studied. The structure refinement after ECAP leads to the formation of elongated Ξ±-Zn grains with a width of ~10 Β΅m and of Mg- and Dy-containing phases. In addition, X-ray diffraction analysis demonstrated that ECAP resulted in the formation of the basal texture in the alloy. These changes in the microstructure and texture lead to an increase in ultimate tensile strength up to 262 Β± 7 MPa and ductility up to 5.7 Β± 0.2%. ECAP slows down the degradation process, apparently due to the formation of a more homogeneous microstructure. It was found that the alloy degradation rate in vivo after subcutaneous implantation in mice is significantly lower than in vitro ones. ECAP does not impair biocompatibility in vitro and in vivo of the Zn-1%Mg-0.1%Dy alloy. No signs of suppuration, allergic reactions, the formation of visible seals or skin ulcerations were observed after implantation of the alloy. This may indicate the absence of an acute reaction of the animal body to the Zn-1%Mg-0.1%Dy alloy in both states
Biocompatibility and Degradation of Fe-Mn-5Si Alloy after Equal-Channel Angular Pressing: In Vitro and In Vivo Study
An attempt to improve the functional characteristics of a degradable Fe-Mn-5Si shape memory alloy by means of structure refinement by equal-channel angular pressing (ECAP) was made. In the course of ECAP, an austenitic ultrafine-grained structure was obtained. In shear bands with a thickness of 301 Β± 31 nm, twins 11 Β± 1 nm in size were formed. Due to the resulting structure, the tensile strength was doubled up to 1419 MPa, and the yield strength was increased up to 1352 MPa, four times higher compared with the annealed state. Dynamic indentation tests revealed a decrease in Youngβs modulus by more than 2.5 times after ECAP compared to values measured in the annealed state. The results of the study of hemolytic and cytotoxic activity in vitro, as well as the local and systemic reactivity of the body of laboratory animals after implantation of the test samples indicate the biocompatibility of the alloy after ECAP. Biocompatibility, high specific strength and low modulus of elasticity open prospects for Fe-Mn-5Si alloy after ECAP to be used for the production of degradable implants that can effectively provide the fastening function in osteoreconstruction
Upconversion Nanoparticles Intercalated in Large Polymer Micelles for Tumor Imaging and Chemo/Photothermal Therapy
Frontiers in theranostics are driving the demand for multifunctional nanoagents. Upconversion nanoparticle (UCNP)-based systems activated by near-infrared (NIR) light deeply penetrating biotissue are a powerful tool for the simultaneous diagnosis and therapy of cancer. The intercalation into large polymer micelles of poly(maleic anhydride-alt-1-octadecene) provided the creation of biocompatible UCNPs. The intrinsic properties of UCNPs (core@shell structure NaYF4:Yb3+/Tm3+@NaYF4) embedded in micelles delivered NIR-to-NIR visualization, photothermal therapy, and high drug capacity. Further surface modification of micelles with a thermosensitive polymer (poly-N-vinylcaprolactam) exhibiting a conformation transition provided gradual drug (doxorubicin) release. In addition, the decoration of UCNP micelles with Ag nanoparticles (Ag NPs) synthesized in situ by silver ion reduction enhanced the cytotoxicity of micelles at cell growth temperature. Cell viability assessment on Sk-Br-3, MDA-MB-231, and WI-26 cell lines confirmed this effect. The efficiency of the prepared UCNP complex was evaluated in vivo by Sk-Br-3 xenograft regression in mice for 25 days after peritumoral injection and photoactivation of the lesions with NIR light. The designed polymer micelles hold promise as a photoactivated theranostic agent with quattro-functionalities (NIR absorption, photothermal effect, Ag NP cytotoxicity, and Dox loading) that provides imaging along with chemo- and photothermal therapy enhanced with Ag NPs