Abstract
An enormous effort has been put into designing nanoparticles (NPs) with controlled biodistributions, prolonged plasma circulation times, and/or enhanced tissue targeting. However, little is known about how to design NPs with precise distributions in the target tissues. In particular, understanding NP tumor penetration and accumulation characteristics is crucial to maximizing the therapeutic potential of drug molecules carried by the NPs. In this study, we employed poly(amidoamine) (PAMAM) dendrimers, given their well-controlled size (<10 nm) and surface charge, to understand how the physical properties of NPs govern their tumor accumulation and penetration behaviors. We demonstrate for the first time that the size and surface charge of PAMAM dendrimers control their distributions in both a 3D multicellular tumor spheroid (MCTS) model and a separate extracellular matrix (ECM) model, which mimics the tumor microenvironment. Smaller PAMAM dendrimers not only diffused more rapidly in the ECM model but also efficiently penetrated to the MCTS core compared to their larger counterparts. Furthermore, cationic, amine-terminated PAMAM dendrimers exhibited the greatest accumulation in MCTS compared to either charge-neutral or anionic dendrimers. Our findings indicate that the size and surface charge of PAMAM dendrimers may tailor their tumor accumulation and penetration behaviors. These results suggest that controlled tumor accumulation and distinct intratumoral distributions can be achieved by simply controlling the size and surface charge of dendrimers, which may also be applicable for other similarly sized NPs.
| Original language | English |
|---|---|
| Pages (from-to) | 2155-2163 |
| Number of pages | 9 |
| Journal | Molecular Pharmaceutics |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2016 Jul 5 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
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Size and surface charge of engineered poly(amidoamine) dendrimers modulate tumor accumulation and penetration : A model study using multicellular tumor spheroids. / Bugno, Jason; Hsu, Hao Jui; Pearson, Ryan M.; Noh, Hyeran; Hong, Seungpyo.
In: Molecular Pharmaceutics, Vol. 13, No. 7, 05.07.2016, p. 2155-2163.Research output: Contribution to journal › Article
TY - JOUR
T1 - Size and surface charge of engineered poly(amidoamine) dendrimers modulate tumor accumulation and penetration
T2 - A model study using multicellular tumor spheroids
AU - Bugno, Jason
AU - Hsu, Hao Jui
AU - Pearson, Ryan M.
AU - Noh, Hyeran
AU - Hong, Seungpyo
PY - 2016/7/5
Y1 - 2016/7/5
N2 - An enormous effort has been put into designing nanoparticles (NPs) with controlled biodistributions, prolonged plasma circulation times, and/or enhanced tissue targeting. However, little is known about how to design NPs with precise distributions in the target tissues. In particular, understanding NP tumor penetration and accumulation characteristics is crucial to maximizing the therapeutic potential of drug molecules carried by the NPs. In this study, we employed poly(amidoamine) (PAMAM) dendrimers, given their well-controlled size (<10 nm) and surface charge, to understand how the physical properties of NPs govern their tumor accumulation and penetration behaviors. We demonstrate for the first time that the size and surface charge of PAMAM dendrimers control their distributions in both a 3D multicellular tumor spheroid (MCTS) model and a separate extracellular matrix (ECM) model, which mimics the tumor microenvironment. Smaller PAMAM dendrimers not only diffused more rapidly in the ECM model but also efficiently penetrated to the MCTS core compared to their larger counterparts. Furthermore, cationic, amine-terminated PAMAM dendrimers exhibited the greatest accumulation in MCTS compared to either charge-neutral or anionic dendrimers. Our findings indicate that the size and surface charge of PAMAM dendrimers may tailor their tumor accumulation and penetration behaviors. These results suggest that controlled tumor accumulation and distinct intratumoral distributions can be achieved by simply controlling the size and surface charge of dendrimers, which may also be applicable for other similarly sized NPs.
AB - An enormous effort has been put into designing nanoparticles (NPs) with controlled biodistributions, prolonged plasma circulation times, and/or enhanced tissue targeting. However, little is known about how to design NPs with precise distributions in the target tissues. In particular, understanding NP tumor penetration and accumulation characteristics is crucial to maximizing the therapeutic potential of drug molecules carried by the NPs. In this study, we employed poly(amidoamine) (PAMAM) dendrimers, given their well-controlled size (<10 nm) and surface charge, to understand how the physical properties of NPs govern their tumor accumulation and penetration behaviors. We demonstrate for the first time that the size and surface charge of PAMAM dendrimers control their distributions in both a 3D multicellular tumor spheroid (MCTS) model and a separate extracellular matrix (ECM) model, which mimics the tumor microenvironment. Smaller PAMAM dendrimers not only diffused more rapidly in the ECM model but also efficiently penetrated to the MCTS core compared to their larger counterparts. Furthermore, cationic, amine-terminated PAMAM dendrimers exhibited the greatest accumulation in MCTS compared to either charge-neutral or anionic dendrimers. Our findings indicate that the size and surface charge of PAMAM dendrimers may tailor their tumor accumulation and penetration behaviors. These results suggest that controlled tumor accumulation and distinct intratumoral distributions can be achieved by simply controlling the size and surface charge of dendrimers, which may also be applicable for other similarly sized NPs.
UR - http://www.scopus.com/inward/record.url?scp=84979026062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979026062&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.5b00946
DO - 10.1021/acs.molpharmaceut.5b00946
M3 - Article
C2 - 26828309
AN - SCOPUS:84979026062
VL - 13
SP - 2155
EP - 2163
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 7
ER -