Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination

Tomás Bauleth-Ramos, Ting-Yu Shih Ting-Yu Shih, Mohammad-Ali Shahbazi, Alexander J. Najibi, Angelo S. Mao, Dongfei Liu, Pedro Granja, Hélder A. Santos, Bruno Sarmento, Danid J. Mooney

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte‐macrophage colony‐stimulating factor and cytosine‐phosphodiester‐guanine‐rich oligonucleotides, are combined with spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), loaded with p53 activator Nutlin‐3a (Nut‐3a) for combined chemoimmunotherapy. The Sp‐AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut‐3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.
Originalspråkengelska
TidskriftAdvanced Functional Materials
Sidor (från-till)1903686
Antal sidor10
ISSN1616-301X
DOI
Status!!Accepted/In press - 27 jun 2019
MoE-publikationstypA1 Tidskriftsartikel-refererad

Citera det här

Bauleth-Ramos, Tomás ; Ting-Yu Shih, Ting-Yu Shih ; Shahbazi, Mohammad-Ali ; Najibi, Alexander J. ; Mao, Angelo S. ; Liu, Dongfei ; Granja, Pedro ; Santos, Hélder A. ; Sarmento, Bruno ; Mooney, Danid J. / Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination. I: Advanced Functional Materials. 2019 ; s. 1903686.
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title = "Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination",
abstract = "Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte‐macrophage colony‐stimulating factor and cytosine‐phosphodiester‐guanine‐rich oligonucleotides, are combined with spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), loaded with p53 activator Nutlin‐3a (Nut‐3a) for combined chemoimmunotherapy. The Sp‐AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut‐3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.",
author = "Tom{\'a}s Bauleth-Ramos and {Ting-Yu Shih}, {Ting-Yu Shih} and Mohammad-Ali Shahbazi and Najibi, {Alexander J.} and Mao, {Angelo S.} and Dongfei Liu and Pedro Granja and Santos, {H{\'e}lder A.} and Bruno Sarmento and Mooney, {Danid J.}",
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Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination. / Bauleth-Ramos, Tomás; Ting-Yu Shih, Ting-Yu Shih; Shahbazi, Mohammad-Ali; Najibi, Alexander J.; Mao, Angelo S.; Liu, Dongfei; Granja, Pedro; Santos, Hélder A.; Sarmento, Bruno ; Mooney, Danid J.

I: Advanced Functional Materials, 27.06.2019, s. 1903686.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - Acetalated Dextran Nanoparticles Loaded into an Injectable Alginate Cryogel for Combined Chemotherapy and Cancer Vaccination

AU - Bauleth-Ramos, Tomás

AU - Ting-Yu Shih, Ting-Yu Shih

AU - Shahbazi, Mohammad-Ali

AU - Najibi, Alexander J.

AU - Mao, Angelo S.

AU - Liu, Dongfei

AU - Granja, Pedro

AU - Santos, Hélder A.

AU - Sarmento, Bruno

AU - Mooney, Danid J.

PY - 2019/6/27

Y1 - 2019/6/27

N2 - Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte‐macrophage colony‐stimulating factor and cytosine‐phosphodiester‐guanine‐rich oligonucleotides, are combined with spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), loaded with p53 activator Nutlin‐3a (Nut‐3a) for combined chemoimmunotherapy. The Sp‐AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut‐3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.

AB - Vaccination represents a promising strategy for cancer therapy due to its ability to efficiently eliminate tumors from the host body and prevent their recurrence. Nevertheless, the current vaccines are still lacking efficacy. Combination therapies, such as those integrating chemotherapy with immunotherapy, represent a powerful tool to potentially circumvent this drawback. Herein, injectable alginate cryogels loaded with granulocyte‐macrophage colony‐stimulating factor and cytosine‐phosphodiester‐guanine‐rich oligonucleotides, are combined with spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), loaded with p53 activator Nutlin‐3a (Nut‐3a) for combined chemoimmunotherapy. The Sp‐AcDEX NPs are successfully loaded into the alginate cryogels and released over time. Furthermore, the delivery of the NPs from the cryogel enhances their accumulation in tumor tissue following peritumoral injection. Nut‐3a exerts toxicity towards the tumor cells and induces immunogenic cell death through the upregulation of surface calreticulin expression. Overall, this combination is a promising strategy to reduce cancer cell proliferation, induce immunogenic cell death, and accumulate drug payloads into the tumor. This approach may avoid cancer recurrence through the induction of in situ cancer vaccination mediated by antigens and danger signals released from the apoptotic cancer cells.

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DO - 10.1002/adfm.201903686

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JO - Advanced Functional Materials

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SN - 1616-301X

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