Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes

Reis, Samara Bonesso dos; Silva, Juliana de Oliveira; Garcia-Fóssa, Fernanda; Leite, Elaine Amaral; Malachias, A.; Pound-Lana, Gwenaelle; Mosqueira, Vanessa Carla Furtado; Oliveira, Mônica Cristina; Barros, André Luís Branco de; Jesus, Marcelo Bispo de

doi:10.1016/j.biopha.2020.110952

Cited by 22 publications

(10 citation statements)

References 34 publications

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“…This difference can be explained by the drug availability in the cell monolayer system used. In fact, in its free form, the whole dosage administered with Dox is immediately available and distributed to the cells by passive diffusion [ 57 ]. Conversely, its administration into NPs implies first the internalization of the delivery system by cells and, then, its release [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery

Gimondi,

Ferreira,

Reis

et al. 2023

IJMS

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Polymeric nanoparticles (NPs) are widely used as drug delivery systems in nanomedicine. Despite their widespread application, a comprehensive understanding of their intracellular trafficking remains elusive. In the present study, we focused on exploring the impact of a 20 nm difference in size on NP performance, including drug delivery capabilities and intracellular trafficking. For that, poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PLGA-PEG) NPs with sizes of 50 and 70 nm were precisely tailored. To assess their prowess in encapsulating and releasing therapeutic agents, we have employed doxorubicin (Dox), a well-established anticancer drug widely utilized in clinical settings, as a model drug. Then, the beneficial effect of the developed nanoformulations was evaluated in breast cancer cells. Finally, we performed a semiquantitative analysis of both NPs’ uptake and intracellular localization by immunostaining lysosomes, early endosomes, and recycling endosomes. The results show that the smaller NPs (50 nm) were able to reduce the metabolic activity of cancer cells more efficiently than NPs of 70 nm, in a time and concentration-dependent manner. These findings are corroborated by intracellular trafficking studies that reveal an earlier and higher uptake of NPs, with 50 nm compared to the 70 nm ones, by the breast cancer cells. Consequently, this study demonstrates that NP size, even in small increments, has an important impact on their therapeutic effect.

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Section: Discussionmentioning

confidence: 99%

Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery

Gimondi,

Ferreira,

Reis

et al. 2023

IJMS

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“…Preparation of Liposome Encapsulated Nanoparticles: The lipid film was prepared according to the method described in the previous literature. [27] Briefly, aliquots of HSPC, cholesterol and DSPE-PEG2000 (5.8:3.7:0.5 molar ratio, at 2 mg mL −1 lipid concentration) were dissolved in chloroform. The liposome solution was dried by rotary evaporation to obtain the lipid film.…”

Section: Methodsmentioning

confidence: 99%

Antigen‐Capturing Dendritic‐Cell–Targeting Nanoparticles for Enhanced Tumor Immunotherapy Based on Photothermal‐Therapy–Induced In Situ Vaccination

Luo

Hou

et al. 2023

Adv Healthcare Materials

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In situ vaccines have revolutionized immunotherapy as they can stimulate tumor‐specific immune responses, with the cancer being the antigen source. However, the heterogeneity of tumor antigens and insufficient dendritic cells (DCs) activation result in low cancer immunogenicity and hence poor vaccine response. Here, a new in situ vaccine composed of acid‐responsive liposome‐coated polydopamine (PDA) nanoparticles modified with mannose and loaded with resiquimod (R848) is designed to promote the efficacy of immunotherapy. The in situ vaccine can actively target the tumor site based on the decomposition of the liposome, while the PDA nanoparticles promote photothermal therapy and capture the immunogenic cell‐death–induced tumor‐associated antigens based on the adsorption effect of dopamine‐mimetic mussels. The PDA nanoparticles, which are modified with a mannose ligand, target the DCs and release R848 for activated antigen presentation. As a result, the in situ vaccine not only effectively activates the maturation of the DCs but also significantly enhances their effect on cytotoxic T lymphocyte cells. Furthermore, the vaccine effectively inhibits the distant recurrence and metastasis of tumors via long‐term immune memory effects. Therefore, the in situ vaccine provides a potential strategy for improving the efficacy of cancer immunotherapy.

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“…Similarly, PSL-DOX resulted in higher nuclear accumulation of DOX in HeLa cells in vitro. This nuclear accumulation was associated with higher activation of cleaved caspase-3 [ 144 ].…”

Section: Ph-sensitive Liposome (Psl)mentioning

confidence: 99%

Recent Preclinical and Clinical Progress in Liposomal Doxorubicin

Aloss

Hamar

2023

Pharmaceutics

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Doxorubicin (DOX) is a potent anti-cancer agent that has garnered great interest in research due to its high efficacy despite dose-limiting toxicities. Several strategies have been exploited to enhance the efficacy and safety profile of DOX. Liposomes are the most established approach. Despite the improvement in safety properties of liposomal encapsulated DOX (in Doxil and Myocet), the efficacy is not superior to conventional DOX. Functionalized (targeted) liposomes present a more effective system to deliver DOX to the tumor. Moreover, encapsulation of DOX in pH-sensitive liposomes (PSLs) or thermo-sensitive liposomes (TSLs) combined with local heating has improved DOX accumulation in the tumor. Lyso-thermosensitive liposomal DOX (LTLD), MM-302, and C225-immunoliposomal(IL)-DOX have reached clinical trials. Further functionalized PEGylated liposomal DOX (PLD), TSLs, and PSLs have been developed and evaluated in preclinical models. Most of these formulations improved the anti-tumor activity compared to the currently available liposomal DOX. However, the fast clearance, the optimization of ligand density, stability, and release rate need more investigations. Therefore, we reviewed the latest approaches applied to deliver DOX more efficiently to the tumor, preserving the benefits obtained from FDA-approved liposomes.

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Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes

Cited by 22 publications

References 34 publications

Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery

Intracellular Trafficking of Size-Tuned Nanoparticles for Drug Delivery

Antigen‐Capturing Dendritic‐Cell–Targeting Nanoparticles for Enhanced Tumor Immunotherapy Based on Photothermal‐Therapy–Induced In Situ Vaccination

Recent Preclinical and Clinical Progress in Liposomal Doxorubicin

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